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202201156 Research Article


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Room-Temperature ZnBr2-Catalyzed Regioselective


1,6-Hydroarylation of Electron-Rich Arenes to para-Quinone
Methides: Synthesis of Unsymmetrical Triarylmethanes
Biquan Xiong,*[a, b] Lulu Si,[a] Longzhi Zhu,*[a, b] Rong Wu,[a] Yu Liu,[a] Weifeng Xu,[a]
Fan Zhang,[c] Ke-Wen Tang,[a] and Wai-Yeung Wong*[b]

Abstract: A mild and efficient Zn(II)-catalyzed regioselective other nucleophiles, such as aniline, indole and phenol
1,6-hydroarylation of para-quinone methides (p-QMs) with derivatives, offering the corresponding triarylmethanes with
electron-rich arenes protocol is reported. A variety of good yields under the standard conditions. The possible
electron-rich arenes and para-quinone methides are well mechanism for the formation of C(sp3) C(sp2) bonds in
tolerated under mild conditions, delivering a broad range of hydroarylation reactions has been explored by step-by-step
triarylmethanes in good to excellent yields. The present control experiments, and the reaction may follow a second-
method also works well for the hydroarylation of p-QMs with order manner in a chemical kinetic study.

Introduction

Triarylmethane derivatives are considered to be a very useful


basic framework, which play an important role in dyes, optical
reagents, fluorescent probes, ligand scaffolds and building
blocks in materials chemistry.[1] In addition, triarylmethane units Figure 1. Important triarylmethane derivatives.
exhibit unique biological activity and widely exist in various
biologically active compounds. As a result, triarylmethane
compounds are also common skeletons in clinical pharmaco- Para-quinone methides (p-QMs) are perceived as an
logical research (Figure 1).[2] Owing to the various application of important and readily available class of highly reactive synthetic
triarylmethanes in these fields, a series of synthetic methods intermediates because of the unique electron-deficient alkene
have been reported for their preparation.[3] Common protocols structure, which are extensively used for the construction of
of constructing triarylmethanes generally include Friedel-Crafts C C and C heteroatom bonds.[5] For example, Deng, Muthuk-
reactions, and transition metal-catalysed C C Suzuki or Kumada rishnan and Li et al. have explored the Lewis acid catalysis or
cross-couplings.[4] These protocols provide triarylmethanes with photochemical catalysis for the construction of various C-
excellent yields and high chemoselectivity. However, some (sp3) C(sp3) bonds through the addition or cyanoalkylation of p-
problems still exist, such as the use of expensive and toxic QMs.[6] Liu and co-workers disclosed the formation of C C
metal salts, low functional group tolerance, as well as the harsh bonds by Cu(II) or Fe(III) catalysis from alkynyl compounds and
reaction conditions, which may limit the widespread use of p-QMs in 2019.[7] Apart from these, Tortosa, Liao and Li et al.
these methods. have provided diverse strategies for making C Si, C B, C S and
C O bonds under Lewis acid, Brønsted acid and transition
metal-catalyzed/mediated conditions, demonstrating the 1,6-
addition possibilities of p-QMs to construct C heteroatom
[a] Dr. B. Xiong, L. Si, Dr. L. Zhu, R. Wu, Dr. Y. Liu, W. Xu, Prof. K.-W. Tang bond.[8] In addition, we also offered a series of novel and
Department of Chemistry and Chemical Engineering
Hunan Institute of Science and Technology
efficient methods for establishing C P and C S bonds through
414006 Yueyang (P. R. China) 1,6-coujugate addition of p-QMs with S and P nucleophiles by
E-mail: [email protected] acid catalysis.[9]
[email protected]
Although the application of p-QMs has been investigated in
[b] Dr. B. Xiong, Dr. L. Zhu, Prof. W.-Y. Wong
Department of Applied Biology and Chemical Technology and Research many organic synthetic fields, the potential of p-QMs as
Institute for Smart Energy building blocks to form triarylmethanes has not been well
The Hong Kong Polytechnic University explored. Recently, there are some examples on constructing
Hung Hom, Hong Kong (P. R. China)
E-mail: [email protected] triarylmethane derivatives via the functionalization of p-QMs
[c] Prof. F. Zhang (Scheme 1a–d). Shi and Anand et al. demonstrated the 1,6-
College of Chemistry and Chemical Engineering conjugate addition/domino electrophilic cyclization and asym-
Jishou University
416000 Jishou (P. R. China)
metric conjugate addition of p-QMs with indoles or o-
Supporting information for this article is available on the WWW under alkynylanilines via chiral phosphoric acid and gold catalysis.[10]
https://doi.org/10.1002/asia.202201156 Out of these protocols, Li and coworkers achieved a protocol

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Research Article

Scheme 1. Approaches for the synthesis of triarylmethanes derived from p-QMs.

for the synthesis of asymmetric triarylmethanes through the ingly, it was found that the target product 3 a was generated in
enantioselective conjugate addition of 2-naphthols to p-QMs 91% yield in DCE solution through the synergetic catalysis of
under chiral phosphoric acid catalysis in 2019.[11] Meanwhile, ZnBr2 (5 mol%) and TMSCl (5 mol%) (Table 1, entry 1). For
Fan and partners studied the 1,6-conjugated reduction of p- further optimization, in addition to DCE as the solvent, we also
QMs for obtaining enantiomerically enriched triarylmethanes by investigated some other solvents, such as EtOAc, CH3CN,
copper catalysis, where Ph2SiH2 and Cu(OAc)2 are adopted to CH3OH, 1,4-dioxane, DMF, toluene, DMSO, THF and DCM
produce the active CuH in situ to promote the reaction.[12] (Table 1, entries 2–10), and 3 a could be constructed in DCM
Therefore, exploring a mild, low-cost and atom-efficient with the highest yield of 96%. For exploring the effect of
regioselective 1,6-hydroarylation of p-QMs is still challenging different catalysts in the reaction, different kinds of Lewis acids,
and demanding. such as ZnCl2, FeCl3, Et2O·BF3, B(C6F5)3, AgBF4, CuBr2 and Cu(OTf)2
In recent years, chemical reactions with mild conditions and were used in the reactions (Table 1, entries 11–17). It is obvious
high atomic economy, as well as the concept of green that ZnBr2 showed the best catalytic activity toward the
chemistry have attracted an increasing attention.[13] Our group’s reaction. The amount of catalyst used also has a great influence
enthusiasm in atom-efficient functionalization of p-QMs encour- on the reaction. When we operated the reaction in the absence
aged us to develop a scheme to build triarylmethanes by the of catalyst, the product 3 a could only be formed in 21% yield
regioselective 1,6-hydroarylation of p-QMs.[14] We focused our (Table 1, entry 18). Meanwhile, the amount of catalyst increased
attention on finding a Lewis acid system which could imple- from 1 mol% to 5 mol% resulted in the sharp increase of the
ment the hydroarylation at ambient temperature.[15] As a yield. However, with a further increase of the amount of catalyst
continuation of this study, we provide a Lewis acids synergetic from 5 mol% to 20 mol%, the yield of 3 a was not greatly
catalysis system for the regioselective 1,6-hydroarylation of p- affected (Table 1, entries 19–21). Based on the above results, we
QMs (Scheme 1e) at room temperature. As far as we know, the further optimized the dosage of TMSCl. When the amount of
direct hydroarylation of p-QMs with electron-rich arenes to form TMSCl was increased from 0 mol% to 20 mol% as the additive,
unsymmetrical triarylmethanes using such catalyst system has the highest yield was obtained with 5 mol% TMSCl (Table 1,
not been reported previously. entries 22–25). When the reaction temperature is increased
from 0 °C to 25 °C, the yield of 3 a could be greatly increased. A
further increase of the temperature lowers the yield of the
Results and Discussion desired product (Table 1, entries 26–29). Thus, after analyzing
the optimization results of a band of reaction conditions, the
Initially, the catalytic system of trimethylsilyl chloride (TMSCl) in optimal reaction condition is as follows: 5 mol% ZnBr2, 5 mol%
combination with various transition metals as catalyst for the TMSCl and DCM as solvent (Table 1, entry 10).
hydroarylation of anisole to p-QMs was explored. The reaction As shown in Table 2, the Zn(II)-catalyzed 1,6-hydroarylation
of 4-benzylidene-2,6-di-tert-butylcyclohexa-2,5-dienone (1 a) reactions of p-QMs with anisole 2 a are suitable for p-QMs with
with anisole (2 a) was selected as the model reaction. Surpris- various substituents, generating the target products in excellent

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Table 1. Optimization of the reaction conditions.[a] Table 2. Substrate scope of p-QMs.[a]

Entry Catalyst Solvent Additive Temp. Yield[b]

1 ZnBr2 (5) DCE TMSCl (5) 25 °C 91%


2 ZnBr2 (5) EtOAc TMSCl (5) 25 °C 28%
3 ZnBr2 (5) CH3CN TMSCl (5) 25 °C 82%
4 ZnBr2 (5) CH3OH TMSCl (5) 25vC ND
5 ZnBr2 (5) 1,4-Dioxane TMSCl (5) 25 °C ND
6 ZnBr2 (5) DMF TMSCl (5) 25 °C ND
7 ZnBr2 (5) PhCH3 TMSCl (5) 25 °C ND
8 ZnBr2 (5) DMSO TMSCl (5) 25 °C ND
9 ZnBr2 (5) THF TMSCl (5) 25 °C ND
10 ZnBr2 (5) DCM TMSCl (5) 25 °C 96%
11 ZnCl2 (5) DCM TMSCl (5) 25 °C 92%
12 FeCl3 (5) DCM TMSCl (5) 25 °C 87%
13 Et2O·BF3 (5) DCM TMSCl (5) 25 °C 89%
14 B(C6F5)3 (5) DCM TMSCl (5) 25 °C 78%
15 AgBF4 (5) DCM TMSCl (5) 25 °C 84%
16 CuBr2 (5) DCM TMSCl (5) 25 °C 43%
17 Cu(OTf)2 (5) DCM TMSCl (5) 25 °C 73%
18 ZnBr2 (0) DCM TMSCl (5) 25 °C 21%
19 ZnBr2 (1) DCM TMSCl (5) 25 °C 74%
20 ZnBr2 (10) DCM TMSCl (5) 25 °C 94%
21 ZnBr2 (20) DCM TMSCl (5) 25 °C 92%
22 ZnBr2 (5) DCM TMSCl (0) 25 °C 42%
23 ZnBr2 (5) DCM TMSCl (1) 25 °C 81%
24 ZnBr2 (5) DCM TMSCl (10) 25 °C 93%
25 ZnBr2 (5) DCM TMSCl (20) 25 °C 91%
26 ZnBr2 (5) DCM TMSCl (5) 0 °C 79%
27 ZnBr2 (5) DCM TMSCl (5) 40 °C 83%
28 ZnBr2 (5) DCM TMSCl (5) 60 °C 77%
29 ZnBr2 (5) DCM TMSCl (5) 80 °C 71% [a] Reaction conditions: anisole (0.2 mmol), p-QMs compounds (0.2 mmol),
ZnBr2 (0.01 mmol), TMSCl (0.01 mmol), DCM (1.0 mL), air, 25 °C, 3 h.
[a] Reaction conditions: 4-benzylidene-2,6-di-tert-butylcyclohexa-2,5-dien-
Isolated yields. [b] Yield was determined by GC analysis.
one (1a, 0.2 mmol), anisole (2a, 0.2 mmol), catalyst (mol %), additive
(mol %) and solvent (1.0 mL) at the indicated temperature for 3 h under
air. [b] Yield was determined by GC analysis, using dodecane as the
internal standard.

of anisole (2 a), the double hydroarylated product 4,4’-(1,4-


phenylenebis((4-methoxyphenyl)methylene))bis(2,6-di-tert-bu-
yield under standard conditions. When p-QMs containing tylphenol) 3 z was obtained in 87% isolated yield. In addition,
electron-donating groups (e. g. 2-Me, 4-Me, 4-Et, 4-t-Bu, 2-OMe, the p-QMs containing heterocycle (1 aa) can also react with
3-OMe, 3-OMe-4-OH, 3,4-di-OMe, 2,5-di-OMe, and 4-OBn) on the anisole (2 a) efficiently to generate 3 aa in 81% yield. According
aryl ring of p-QMs (Table 2, 1 b–1 k) reacted with anisole (2 a), to the above results of the 1,6-hydroarylation of the various
the desired products 3 b–3 k could be obtained in good to substituted p-QMs with anisole, it is clear that the p-QMs with
excellent yields (78–94%). In order to further investigate the different electron densities, such as electron-withdrawing,
functional group tolerance of the 1,6-hydroarylation reaction, a electron-donating substituents, and heterocycle exhibited high
train of p-QMs with different electron-withdrawing substituents reactivity in the transformation.
(e. g. 2-F, 3-F, 4-F, 2-Br, 3-Br, 4-Br, 3-CN, 4-CN, 4-CHO, and 4-CF3) As illustrated in Table 3, to further study the substrate scope
on the aryl ring (Table 2, 1 l–1 u) reacting with anisole were of the reaction, the 1,6-hydroarylation reaction with respect to
operated under standard conditions. The 1,6-hydroarylated anisole derivatives continues to be examined. It is obvious that
products 3 l–3 u were obtained in 76–94% isolated yields. To anisole derivatives with electron-donating groups such as 1,2-
our delight, the p-QMs with nitro group on the benzene ring dimethoxybenzene (2 b), 1-(tert-butyl)-2-methoxybenzene (2 c),
(1 v) is also well tolerated in the transformation, leading to the 1-isopropyl-2-methoxybenzene (2 d), 1-ethyl-2-methoxybenzene
formation of the corresponding product 3 v in 93%. Moreover, (2 e), 1-methoxy-2-methylbenzene (2 f), 1,3-dimethoxybenzene
through the 1,6-hydroarylation reaction of the substrates 1 w– (2 g), 1-isopropyl-3-methoxybenzene (2 h), 1,3-diisopropyl-2-
1 y with anisole (2 a), the expected products 4-((4-meth- methoxybenzene (2 i), 2-methoxy-1,3-dimethylbenzene (2 j) and
oxyphenyl)(phenyl)methyl)-2,6-dimethylphenol (3 w), 2,6-diiso- 1,2,3-trimethoxybenzene (2 k) exhibit high reactivity toward 4-
propyl-4-((4-methoxyphenyl)(phenyl)methyl)phenol (3 x), and benzylidene-2,6-di-tert-butylcyclohexa-2,5-dienone (1 a), gener-
5’-((4methoxyphenyl)(phenyl)methyl)-[1,1’:3’,1’’-terphenyl]-2’-ol ating the target products 4 a–4 j in 72–94% yields. Meanwhile,
(3 y) were generated in 82–90% isolated yields under standard 4-allyl-5-((3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl)-2-
conditions. Interestingly, when 1 z reacts with two equivalents methoxyphenol (4 k), 4-((2-allyl-4,5-dimeth-

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Table 3. Substrate scope of anisoles.[a] substrates which contain halogen atoms, alkene or alkyne
groups, can be further functionalized into more complex and
useful molecules.
As depicted in Table 4, in order to investigate the applic-
ability of this protocol, phenol (5 a), o-cresol (5 b), 2-bromophe-
nol (5 c) and naphthalen-2-ol (5 d) were allowed to react with
1 a, the intended products 6 a–6 d could be obtained in 76–90%
yields. The indole substrates 5 e–5 h also have excellent
reactivity at the C3 position, generating the target products
6 e–6 h in 86–92% yields. Meanwhile, the expected products 6 i–
6 k could be obtained in 76–83% yields through the reactions of
anilines (5 i, 5 j, 5 k,) with 1 a. Due to the strong nucleophilicity
of the amino group, the 1,6-conjugate addition of 1 a with
aniline (5 l) proceeded at the amino group, generating 6 l in
87% yield. When naphthyl compounds such as 1-meth-
oxynaphthalene (5 m) and 2-methoxynaphthalene (5 n) were
employed as the substrates for the reaction under the
optimized reaction conditions, the products 6 m and 6 n could
be synthesized in 76% and 80% yields, respectively. Interest-
ingly, the reaction of methyl(m-tolyl)sulfane (5 o) can also react
with 1 a to provide the corresponding product 6 o in 78% yield.
Besides these general substrates, we further adopted hetero-
cyclic thiophene ether (5 p) and thiophene thioether (5 q) as the
substrates to react with 1 a under the standard conditions, the
expected products 6 p and 6 q were produced as we expected
in 73% and 69% yields, respectively. However, when 4-meth-
oxypyridine (5 r), furan (5 s) and 2-methylfuran (5 t) are used as
raw materials, as monitored by GC-MS and NMR analysis, it is

oxyphenyl)(phenyl)methyl)-2,6-di-tert-butylphenol (4 l) and 4- Table 4. [a] Reaction conditions: 1 a (0.2 mmol), anisoles (2 b–ac,
0.2 mmol), ZnBr2 (0.01 mmol), TMSCl (0.01 mmol), DCM (1.0 mL), air, 25 °C,
((2-bromo-4,5-dimethoxyphenyl)(phenyl)methyl)-2,6-di-tert-bu- 3 h. Isolated yields.Table 4
tylphenol (4 m) were obtained in 73–87% yields through the Scope of other reactive substrates.[a]
reactions of 1 a with anisole derivatives 2 l–2 n under the
present reaction conditions. Additionally, the halogen function-
alized anisoles, such as 1-fluoro-2-methoxybenzene (2 o), 1-
chloro-2-methoxybenzene (2 p), 1-bromo-2-methoxybenzene
(2 q), 1-fluoro-3-methoxybenzene (2 r), 1-chloro-3-meth-
oxybenzene (2 s), 1-bromo-3-methoxybenzene (2 t) and 1-iodo-
3-methoxybenzene (2 u) also showed satisfactory results, pro-
ducing the 1,6-hydroarylation products 4 n–4 t with good to
excellent yields. For the products 4 q–4 t, since the methoxy
group has a stronger orienting effect than halogen on the aryl
ring, the above products become the only products in the
reaction. Meanwhile, 2-methoxy-1,1’-biphenyl (2 v), and 2-meth-
oxybenzaldehyde (2 w) also show good to excellent reactivity in
the reaction with the expected target products 4 u and 4 v
synthesized in 93% and 69% yield, respectively. Apart from
methoxybenzene, other analogues, such as ethoxybenzene
(2 x), propoxybenzene (2 y), (benzyloxy)benzene (2 z),
(allyloxy)benzene (2 aa), (prop-2-yn-1-yloxy)benzene (2 ab) and
oxydibenzene (2 ac) also works well in the reaction, generating
the corresponding products 4 w–4 ab in 74–92% yields. In other
common Lewis acid-catalyzed reactions involving anisole,
anisole is easy to be substituted in the ortho position, while in
the present zinc-catalyzed system, high para-position regiose-
lectivity is observed.[16] It is worth pointing out that the above

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Scheme 2. Large-scale synthesis and selective functionalization of 3 o.

very difficult to form the corresponding target products (6 r–6 t)


after the reaction.
To better demonstrate the practical application of this
method, a gram-scale synthesis of 3 o was performed by the
zinc(II)-catalyzed 1,6-hydroarylation reaction of 4-((3,5-di-tert-
butyl-4-oxocyclohexa-2,5-dien-1-ylidene)methyl)benzaldehyde
(1 o, 10 mmol) with anisole (2 a, 10 mmol). The expected
product 3 o was produced in 63% yield (2.71 g) after purifica-
tion, satisfying the practical application requirements (Sche- Figure 2. (A): Reaction yield of 3 a, 6 a, 6 e, 6 i and 6 l versus the reaction
me 2A). Because the aldehyde group in 3 o has good reactivity, time. (B): the reaction order of the reaction was expressed by the relation-
ship between (1/CA-1/CA0) and time.
a whole train of functionalization reactions based on the
aldehyde group were run by the selective modifications,
inducing various kinds of functional groups without affecting
the core motif of 3 o (Scheme 2B). Addition of diphenyl proceeded with very high reaction rate and the yield of product
phosphine oxide (7 a’) to the aldehyde group in 3 o, namely the 3 a, 6 e could reach to the highest 95% and 91% yields within
Pudovik reaction, the reaction can also delivere the hydroxyl 3 hours, respectively. The product 6 a was obtained up to 90%
phosphorus compound 7 a in 78% yield via Cs2CO3 catalysis. In yield at 4 hours under the standard reaction condition.
addtion, the reactions of 3 o with 1-bromobut-2-yne (7 b’) and However, the product 6 l was produced with an optimal yield of
ethynylbenzene (7 c’) were carried out, and the corresponding 87% at 8 hours, and 6 i reached its best 82% yield at 10 hours,
nucleophilic addition products 7 b and 7 c were obtained in in which the reaction rates were significantly lower than that of
91% and 82% yields, respectively. Along with the addition of 3 a, 6 a and 6 e.
malononitrile (7 d’), the selective modifications of 3 o provided To further explore the reaction order of the above reactions,
the alkene product 7 d in 75% yield. In addition, 3 o could react a series of tracking experiments were detected by GC analysis.
efficiently with benzene-1,2-diamine (7 e’) to produce the 2-aryl The detected data were calculated and analyzed through the
benzimidazole 7 e in 93% yield when CuSO4 was used as the integral formula of the second-order reaction kinetics (1/CA-1/
catalyst to promote the reaction. To our surprise, when 3 o CA0) = k’t:
reacted with two equivalents of indole (7 f’), the (1) Reaction impedance rate equation: rA ¼ kCA CB
bis(indole)methane compound 7 f was generated in 73% yield
by H2SO4 catalysis. dCA dx
¼ CA0 A ¼ kCA0 ð1 xA ÞðCB0 CA0 xA Þ
In order to further understand the reaction, we monitored dt dt
the reaction process by GC and 1H NMR analysis as shown in
C
Figure 2. According to the chemical kinetics results stated in (2) Initial concentration ratio: M ¼ CA0B0
Figure 2A, the reaction of 1 a with anisole (2 a) and indole (5 e)

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Scheme 3. Control experiments.

Z xA
Z t
dxA
¼ kCA0 dt
0 ð1 xA ÞðM xA Þ 0 71% yield (Scheme 3, eq. 5). Besides, we further explored the
competitive reaction which involves the hydroarylation of p-
QMs (1 a) with aniline and N,N-dimethylaniline in a one-pot
(3) The initial concentration ratio satisfies: CA0 ¼ CB0 , so, reaction under standard conditions, the products 6 i and 6 l
M¼1 could be synthesized in 87.1% and 7.9% yields as confirmed by
(4) The above formula can be transformed into: GC and 1H NMR analysis (Scheme 3, eq. 6). The result shows that
� � the compound 5 i has a higher nucleophilicity, which has a
1 1 0
CA CA0 ¼ k t
better reactivity than the compound 5 l in the competitive
Graphs of relation were depicted in the variable relationship reaction.
between (1/CA-1/CA0) at different time (Figure 2B). Since the Based on the above experimental results and previous
graphics of relationship of (1/CA-1/CA0) versus t fits well with a studies, a plausible mechanism is described as shown in
straight line, the experimental results show that reaction Scheme 4.[15a] First, ZnBr2 initially activates the C=O group of p-
process of 3 a, 6 a, 6 e, 6 i and 6 l probably follows the second- QMs (1 a) to form the intermediate (A). Then, the para C H
order reaction.[17] bond of anisole (2 a) reacts with the electron-deficient A,
In order to explore the reaction mechanism, a series of generating the arenium ion (B) via the 1,6-conjugated addition/
control experiments were implemented under standard con- aromatization processes. Subsequently, the possible intermedi-
ditions. When the free-radical scavenger 2,2,6,6-tetrameth- ate C was generated through the deprotonation reaction of B
ylpiperidine N-oxyl (TEMPO) was added to the reaction under with TMSCl, with the release of hydrogen chloride and zinc (II)
standard reaction conditions, to our surprise, 3 a could still be cation. Finally, the target product 3 a was obtained through the
formed in 82% yield (Scheme 3, eq. 1). Therefore, the reaction acidification of the hydrogen chloride. It is worth noting that
may be established not through a free radical mechanism. In the released zinc source and the regenerated TMSCl could be
addition, when 2,6-di-tert-butyl-4-methylphenol (BHT) was used reused to the next catalytic cycle.
as the radical inhibitor for the reaction under standard reaction
conditions, the hydroarylation product 3 a could be isolated in
91% yield (Scheme 3, eq. 2). On the other hand, when HCl was
used to replace TMSCl for the reaction, the expected product
3 a could be obtained in 92% yield (Scheme 3, eq. 3), indicating
that TMSCl presumably promotes the reaction by releasing HCl
to act as a Brønsted acid.[15a] Meanwhile, for proving the transfer
mechanism of hydrogen atom in the reaction process, CDCl3 as
the reaction solvent for the hydroarylation of phenol-d6 with p-
QMs (1 a) was performed (Scheme 3, eq. 4). However, because
the deuterated hydrogen atom of hydroxyl was very easy to be
replaced by hydrogen atoms from water and air, the retention
ratio of the deuterated atom of hydroxyl was only 30% after the
purification. The results show that the keto-enol tautomerism
may occur during the reaction. When one equivalent of H2O
was used to replace 2 a to react with 1 a under standard
conditions, 1 a first forms electron deficient intermediate by the
activation of catalytic system and then H2O attacked the
electron deficient intermediate to provide the product 3 a’ in Scheme 4. A plausible reaction mechanism.

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Research Article
In summary, we have demonstrated a facile and practical 34.4 (s), 30.4 (s), 21.1 (s). HRMS (ESI) m/z: calcd. For C29H37O2 [M +
protocol for the construction of triarylmethane products H] + : 417.2789, found: 417.2785.
through the zinc-catalyzed regioselective 1,6-hydroarylation of 2,6-Di-tert-butyl-4-((4-ethylphenyl)(4-methoxyphenyl) meth-
para-quinone methides with electron-rich arenes. A series of yl)phenol (3 c). According to the general procedure, work-up and
the corresponding 1,6-hydroarylation products were obtained flash column chromatography (Rf = 0.5, Hexane/EtOAc: 30 : 1),
in good yields and with high regioselectivity under mild product 3 c (72.3 mg, 0.168 mmol, 84%) was obtained as a yellow
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.08–7.10 (m, 2 H),
conditions. The salient features of this protocol include the high
7.00–7.04 (m, 4 H), 6.91 (s, 2 H), 6.79–6.82 (m, 2 H), 5.35 (s, 1 H), 5.06
efficiency, mild reaction condition and excellent functional (s, 1 H), 3.78 (s, 3 H), 2.59–2.64 (m, 2 H), 1.36 (s, 18 H), 1.21 (t, J =
group tolerance. As far as we know, the regioselective hydro- 7.4 Hz, 3 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS):δ = 157.7 (s),
arylation of p-QMs with anisoles by zinc catalysis has not been 152.0 (s), 142.4 (s), 141.7 (s), 137.4 (s), 135.3 (s), 134.6 (s), 130.3 (s),
reported previously. Furthermore, other nucleophiles, such as 129.2 (s), 127.6 (s), 126.0 (s), 113.4 (s), 55.7 (s), 55.2 (s), 34.4 (s),
phenols, naphthols, indoles, and amines are workable in the 30.4 (s), 28.4 (s), 15.6 (s). HRMS (ESI) m/z: calcd. For C30H39O2 [M +
H] + : 431.2945, found: 431.2939.
reaction system, generating a variety of active functional group
substituted products in good to excellent yields. This method 2,6-Di-tert-butyl-4-((4-(tert-butyl)phenyl)(4-methoxyphenyl) meth-
exhibits a high potential value in synthesizing high value-added yl)phenol (3 d). According to the general procedure, work-up and
flash column chromatography (Rf = 0.4, Hexane/EtOAc: 30 : 1),
triarylmethane derivatives, which may have good application in
product 3 d (83.5 mg, 0.182 mmol, 91%) was obtained as a yellow
medicinal chemistry and functional materials research. oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.26–7.28 (m, 2 H),
7.01–7.04 (m, 4 H), 6.91 (s, 2 H), 6.80–6.82 (m, 2 H), 5.34 (s, 1 H), 5.05
(s, 1 H), 3.78 (s, 3 H), 1.36 (s, 18 H), 1.29 (s, 9 H). 13C NMR (100 MHz,
Experimental Section CDCl3, 25 °C, TMS):δ = 157.7 (s), 152.0 (s), 148.6 (s), 142.0 (s),
137.4 (s), 135.3 (s), 134.6 (s), 130.3 (s), 128.8 (s), 126.0 (s), 124.9 (s),
113.4 (s), 55.6 (s), 55.2 (s), 34.4 (s), 34.3 (s), 31.4 (s), 30.3 (s). HRMS
General Information
(ESI) m/z: calcd. For C32H43O2 [M + H] + : 459.3258, found: 459.3250.
All solvents used in the reactions were freshly distilled. The other 4-((4-(Benzyloxy)phenyl)(4-methoxyphenyl)methyl)-2,6-di-tert-butyl
reagents were recrystallized or distilled as necessary. 1H (400 MHz), phenol (3 e). According to the general procedure, work-up and flash
13 1
C{ H} (100 MHz), 31P{1H} (160 MHz) and 19F{1H} (376 MHz) were column chromatography (Rf = 0.5, Hexane/EtOAc: 20 : 1), product 3 e
recorded on a 400 MHz spectrometer in CDCl3. 1H NMR chemical (84.4 mg, 0.166 mmol, 83%) was obtained as a yellow oil. 1H NMR
shifts were reported using TMS (tetramethyl silane) as the internal (400 MHz, CDCl3, 25 °C, TMS): δ = 7.41–7.43 (m, 2 H), 7.35–7.39 (m,
standard while 13C NMR chemical shifts were reported relative to 2 H), 7.29–7.33 (m, 1 H), 7.00–7.02 (m, 4 H), 6.87–6.89 (m, 4 H), 6.80–
CDCl3. 6.82 (m, 2 H), 5.33 (s, 1 H), 5.06 (s, 1 H), 5.04 (s, 2 H), 3.78 (s, 3 H),
1.36 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 157.8 (s),
157.0 (s), 152.0 (s), 137.7 (s), 137.4 (s), 137.2 (s), 135.4 (s), 134.8 (s),
General procedure for the regioselective 1,6-hydroarylation
130.2 (s), 130.2 (s), 128.6 (s), 127.9 (s), 127.5 (s), 125.9 (s), 114.4 (s),
reaction
113.5 (s), 70.0 (s), 55.2 (s), 55.2 (s), 34.3 (s), 30.4 (s). HRMS (ESI) m/z:
A mixture of para-quinone methides (p-QMs) (0.2 mmol), electron- calcd. For C35H41O3 [M + H] + : 509.3051, found: 509.3044.
rich arenes (0.2 mmol), ZnBr2 (5 mol%) and TMSCl (5 mol%) were
2,6-Di-tert-butyl-4-((4-methoxyphenyl)(o–tolyl)methyl) phenol (3 f).
dissolved in DCM (1 mL) under air atmosphere, and stirred for 3.0 h
According to the general procedure, work-up and flash column
at 25 °C. Upon completion of the reaction, the mixture was
chromatography (Rf = 0.5, Hexane/EtOAc: 30 : 1), product 3 f
concentrated under vacuum, giving the crude product. A pure
(72.5 mg, 0.174 mmol, 87%) was obtained as a yellow oil. 1H NMR
product was obtained by passing the crude product through a
(400 MHz, CDCl3, 25 °C, TMS): δ = 7.09–7.14 (m, 3 H), 6.95–6.97 (m,
short silica gel column using hexane/EtOAc (10 : 1–20 : 1) as eluent.
2 H), 6.79–6.83 (m, 5 H), 5.50 (s, 1 H), 5.06 (s, 1 H), 3.78 (s, 3 H), 2.21
2,6-Di-tert-butyl-4-((4-methoxyphenyl)(phenyl)methyl) phenol (3 a). (s, 3 H), 1.35 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ =
According to the general procedure, work-up and flash column 157.7 (s), 152.0 (s), 143.6 (s), 136.5 (s), 136.3 (s), 135.4 (s), 134.0 (s),
chromatography (Rf = 0.4, Hexane/EtOAc: 30 : 1), product 3 a 130.4 (s), 130.2 (s), 129.2 (s), 126.2 (s), 126.0 (s), 125.6 (s), 113.5 (s),
(75.7 mg, 0.188 mmol, 94%) was obtained as a yellow oil.[12b] 55.2 (s), 52.6 (s), 34.23 (s), 30.4 (s), 20.0 (s). HRMS (ESI) m/z: calcd. For
1
H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.23–7.27 (m, 2 H), 7.15– C29H37O2 [M + H] + : 417.2789, found: 417.2784.
7.18 (m, 1 H), 7.10–7.12 (m, 2 H), 7.01–7.03 (m, 2 H), 6.90 (s, 2 H),
2,6-Di-tert-butyl-4-((2-methoxyphenyl)(4-methoxyphenyl) meth-
6.80–6.82 (m, 2 H), 5.39 (s, 1 H), 5.06 (s, 1 H), 3.77 (s, 3 H), 1.36 (s,
yl)phenol (3 g). According to the general procedure, work-up and
18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 157.9 (s), 152.1 (s),
flash column chromatography (Rf = 0.4, Hexane/EtOAc: 30 : 1),
145.2 (s), 137.1 (s), 135.5 (s), 134.5 (s), 130.4 (s), 129.4 (s), 128.41 (s),
product 3 g (77.0 mg, 0.178 mmol, 89%) was obtained as a yellow
126.0 (s), 126.0 (s), 113.5 (s), 56.1 (s), 55.3 (s), 34.4 (s), 30.4 (s).
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.16–7.20 (m, 1 H),
2,6-Di-tert-butyl-4-((4-methoxyphenyl)(p–tolyl)methyl) phenol (3 b). 6.98–7.01 (m, 2 H), 6.84–6.88 (m, 5 H), 6.77–6.79 (m, 2 H), 5.76 (s,
According to the general procedure, work-up and flash column 1 H), 5.03 (s, 1 H), 3.77 (s, 3 H), 3.71 (s, 3 H), 1.35 (s, 18 H). 13C NMR
chromatography (Rf = 0.4, Hexane/EtOAc: 30 : 1), product 3 b (100 MHz, CDCl3, 25 °C, TMS): δ = 157.5 (s), 157.1 (s), 151.9 (s),
(76.7 mg, 0.184 mmol, 92%) was obtained as a yellow oil. 1H NMR 137.0 (s), 135.2 (s), 134.3 (s), 133.9 (s), 130.2 (s), 130.2 (s), 127.1 (s),
(400 MHz, CDCl3, 25 °C, TMS): δ = 6.99–7.08 (m, 6 H), 6.91–6.92 (m, 126.1 (s), 120.2 (s), 113.3 (s), 110.7 (s), 55.7 (s), 55.2 (s), 48.5 (s),
2 H), 6.79–6.81 (m, 2 H), 5.36 (s, 1 H), 5.06 (s, 1 H), 3.76 (s, 3 H), 2.31 34.3 (s), 30.4 (s). HRMS (ESI) m/z: calcd. For C29H37O3 [M + H] + :
(s, 3 H), 1.36 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 433.2738, found: 433.2731.
157.8 (s), 152.0 (s), 142.3 (s), 137.4 (s), 135.4 (s), 134.7 (s), 130.3 (s),
2,6-Di-tert-butyl-4-((3-methoxyphenyl)(4-methoxyphenyl) meth-
129.2 (s), 128.9 (s), 126.0 (s), 113.9 (s), 113.5 (s), 55.7 (s), 55.3 (s),
yl)phenol (3 h). According to the general procedure, work-up and
flash column chromatography (Rf = 0.4, Hexane/EtOAc: 30 : 1),

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Research Article
product 3 h (73.5 mg, 0.170 mmol, 85%) was obtained as a yellow 6.96–7.00 (m, 4 H), 6.86 (s, 2 H), 6.80–6.83 (m, 2 H), 5.34 (s, 1 H), 5.09
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.16–7.20 (m, 1 H), (s, 1 H), 3.78 (s, 3 H), 1.36 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C,
7.02–7.04 (m, 2 H), 6.91 (s, 2 H), 6.79–6.82 (m, 2 H), 6.70–6.74 (m, TMS): δ = 158.0 (s), 152.2 (s), 144.4 (s), 136.4 (s), 135.6 (s), 133.9 (s),
2 H), 6.66–6.67 (m, 1 H), 5.35 (s, 1 H), 5.07 (s, 1 H), 3.77 (s, 3 H), 3.73 131.2 (s), 131.1 (s), 130.2 (s), 125.9 (s), 119.8 (s), 113.6 (s), 55.4 (s),
(s, 3 H), 1.36 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 55.3 (s), 34.4 (s), 30.3 (s). HRMS (ESI) m/z: calcd. For C28H34BrO2 [M +
159.5 (s), 157.8 (s), 152.1 (s), 146.9 (s), 136.9 (s), 135.4 (s), 134.3 (s), H] + : 481.1737, found: 481.1731.
130.3 (s), 129.0 (s), 126.0 (s), 122.0 (s), 115.4 (s), 113.5 (s), 111.1 (s),
56.0 (s), 55.2 (s), 55.1 (s), 34.4 (s), 30.4 (s). HRMS (ESI) m/z: calcd. For 4-((3,5-Di-tert-butyl-4-hydroxyphenyl)(4-methoxyphenyl) meth-
C29H37O3 [M + H] + : 433.2738, found: 433.2733. yl)benzonitrile (3 n). According to the general procedure, work-up
and flash column chromatography (Rf = 0.5, Hexane/EtOAc: 20 : 1),
2,6-Di-tert-butyl-4-((4-hydroxy-3-methoxyphenyl)(4-meth- product 3 n (72.3 mg, 0.176 mmol, 88%) was obtained as a yellow
oxyphenyl)methyl)phenol (3 i). According to the general procedure, oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): 7.54–7.56 (m, 2 H), 7.21–
work-up and flash column chromatography (Rf = 0.5, Hexane/EtOAc: 7.23 (m, 2 H), 6.97–7.00 (m, 2 H), 6.82–6.84 (m, 4 H), 5.43 (s, 1 H),
20 : 1), product 3 i (70.0 mg, 0.156 mmol, 78%) was obtained as a 5.14 (s, 1 H), 3.78 (s, 3 H), 1.36 (s, 18 H). 13C NMR (100 MHz, CDCl3,
yellow oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.00–7.02 (m, 25 °C, TMS): δ = 158.2 (s), 152.5 (s), 151.0 (s), 135.8 (s), 135.4 (s),
2 H), 6.91 (s, 2 H), 6.80–6.82 (m, 3 H), 6.63 (s, 1 H), 6.56–6.58 (m, 1 H), 133.1 (s), 132.0 (s), 130.3 (s), 130.1 (s), 125.9 (s), 119.2 (s), 113.8 (s),
5.52 (s, 1 H), 5.31 (s, 1 H), 5.07 (s, 1 H), 3.78 (s, 3 H), 3.76 (s, 3 H), 1.35 109.8 (s), 56.1 (s), 55.3 (s), 34.4 (s), 30.3 (s). HRMS (ESI) m/z: calcd. For
(s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 157.8 (s), C29H34NO2 [M + H] + : 428.2585, found: 428.2580.
152.0 (s), 146.2 (s), 143.7 (s), 137.4 (s), 137.2 (s), 135.4 (s), 134.7 (s),
130.2 (s), 125.9 (s), 122.1 (s), 114.0 (s), 113.5 (s), 112.1 (s), 55.9 (s), 4-((3,5-Di-tert-butyl-4-hydroxyphenyl)(4-methoxyphenyl) meth-
55.6 (s), 55.2 (s), 34.4 (s), 30.4 (s). HRMS (ESI) m/z: calcd. For C29H37O4 yl)benzaldehyde (3 o). According to the general procedure, work-up
[M + H] + : 449.2687, found: 449.2683. and flash column chromatography (Rf = 0.5, Hexane/EtOAc: 20 : 1),
product 3 o (65.4 mg, 0.152 mmol, 76%) was obtained as a yellow
2,6-Di-tert-butyl-4-((3,4-dimethoxyphenyl)(4-methoxyphenyl)meth- oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 9.97 (s, 1 H), 7.78–7.80
yl)phenol (3 j). According to the general procedure, work-up and (m, 2 H), 7.28–7.30 (m, 2 H), 7.00–7.02 (m, 2 H), 6.88 (s, 2 H), 6.82–
flash column chromatography (Rf = 0.5, Hexane/EtOAc: 30 : 1), 6.84 (m, 2 H), 5.46 (s, 1 H), 5.12 (s, 1 H), 3.79 (s, 3 H), 1.36 (s, 18 H).
13
product 3 j (73.1 mg, 0.158 mmol, 79%) was obtained as a yellow C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 192.1 (s), 158.1 (s),
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.00–7.03 (m, 2 H), 152.6 (s), 152.4 (s), 135.8 (s), 135.8 (s), 134.5 (s), 133.4 (s), 130.3 (s),
6.91 (s, 2 H), 6.76–6.82 (m, 3 H), 6.66 (s, 1 H), 6.60–6.62 (m, 1 H), 5.32 130.0 (s), 129.7 (s), 125.9 (s), 113.8 (s), 56.2 (s), 55.3 (s), 34.4 (s),
(s, 1 H), 5.06 (s, 1 H), 3.85 (s, 3 H), 3.79 (s, 3 H), 3.76 (s, 3 H), 1.36 (s, 30.3 (s). HRMS (ESI) m/z: calcd. For C29H35O3 [M + H] + : 431.2581,
18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 157.8 (s), 152.0 (s), found: 431.2574.
148.6 (s), 147.2 (s), 137.8 (s), 137.4 (s), 135.4 (s), 134.6 (s), 130.2 (s),
125.9 (s), 121.4 (s), 113.5 (s), 112.7 (s), 110.7 (s), 55.8(s), 55.8 (s), 2,6-Di-tert-butyl-4-((4-methoxyphenyl)(4-(trifluoromethyl)
55.5 (s), 55.2 (s), 34.4 (s), 30.4 (s). HRMS (ESI) m/z: calcd. For C30H39O4 phenyl)methyl)phenol (3 p). According to the general procedure,
[M + H] + : 463.2843, found: 463.2838. work-up and flash column chromatography (Rf = 0.4, Hexane/EtOAc:
20 : 1), product 3 p (82.8 mg, 0.176 mmol, 88%) was obtained as a
2,6-Di-tert-butyl-4-((2,5-dimethoxyphenyl)(4-methoxyphenyl)meth- yellow oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.51–7.53 (m,
yl)phenol (3 k). According to the general procedure, work-up and 2 H), 7.21–7.23 (m, 2 H), 7.00–7.02 (m, 2 H), 6.88 (s, 2 H), 6.82–6.84
flash column chromatography (Rf = 0.5, Hexane/EtOAc: 30 : 1), (m, 2 H), 5.44 (s, 1 H), 5.11 (s, 1 H), 3.77 (s, 3 H), 1.36 (s, 18 H).
13
product 3 k (74.0 mg, 0.160 mmol, 80%) was obtained as a yellow C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 158.1 (s), 152.4 (s),
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.00–7.02 (m, 2 H), 149.4 (s), 136.1 (s), 135.7 (s), 133.6 (s), 130.3 (s), 129.7 (s), 128.3 (d,
1
6.89 (s, 2 H), 6.77–6.79 (m, 3 H), 6.68–7.71 (m, 1 H), 6.48–6.49 (m, J(C,F) = 32.1 Hz), 125.9 (s), 125.1 (d, 1J(C,F) = 3.8 Hz), 124.4 (d,
1
1 H), 5.73 (s, 1 H), 5.03 (s, 1 H), 3.77 (s, 3 H), 3.66 (s, 3 H), 3.64 (s, 3 H), J(C,F) = 270.1 Hz), 113.7 (s), 55.9 (s), 55.3 (s), 34.4 (s), 30.3 (s). 19F
1.35 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 157.6 (s), {1H} NMR (376 MHz, CDCl3, 25 °C, TMS): δ = 62.2 (s). HRMS (ESI)
153.4 (s), 151.9 (s), 151.6 (s), 136.7 (s), 135.4 (s), 135.2 (s), 134.1 (s), m/z: calcd. For C29H34F3O2 [M + H] + : 471.2506, found: 471.2499.
130.2 (s), 126.1 (s), 117.0 (s), 113.3(s), 112.0 (s), 111.0 (s), 56.5 (s),
2,6-Di-tert-butyl-4-((2-fluorophenyl)(4-methoxyphenyl) meth-
55.6 (s), 55.2 (s), 48.8 (s), 34.3 (s), 30.4 (s). HRMS (ESI) m/z: calcd. For
yl)phenol (3 q). According to the general procedure, work-up and
C30H39O4 [M + H] + : 463.2843, found: 463.2837.
flash column chromatography (Rf = 0.5, Hexane/EtOAc: 20 : 1),
2,6-Di-tert-butyl-4-((4-fluorophenyl)(4-methoxyphenyl) meth- product 3 q (70.7 mg, 0.168 mmol, 84%) was obtained as a yellow
yl)phenol (3 l). According to the general procedure, work-up and oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.14–7.20 (m, 1 H),
flash column chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1), 6.93–7.03 (m, 5 H), 6.89 (s, 2 H), 6.80–6.82 (m, 2 H), 5.68 (s, 1 H), 5.08
product 3 l (72.3 mg, 0.172 mmol, 86%) was obtained as a yellow (s, 1 H), 3.77 (s, 3 H), 1.36 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C,
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.04–7.07 (m, 2 H), TMS): δ = 160.7 (d, 1J(C,F) = 244.9 Hz), 157.9 (s), 152.2 (s), 135.7 (s),
6.99–7.01 (m, 2 H), 6.92–6.96 (m, 2 H), 6.87 (s, 2 H), 6.80–6.83 (m, 135.5 (s), 133.1 (s), 132.3 (d, 1J(C,F) = 14.2 Hz), 130.8 (d, 1J(C,F) =
2 H), 5.37 (s, 1 H), 5.08 (s, 1 H), 3.77 (s, 3 H), 1.36 (s, 18 H). 13C NMR 4.1 Hz), 130.1 (s), 127.8 (d, 1J(C,F) = 8.1 Hz), 125.9 (s), 123.7 (d,
(100 MHz, CDCl3, 25 °C, TMS): δ = 161.3 (d, 1J(C,F) = 242.7 Hz), 1
J(C,F) = 3.5 Hz), 115.2 (d, 1J(C,F) = 22.2 Hz), 113.6 (s), 55.2 (s), 48.4 (s),
157.9 (s), 152.1 (s), 141.0 (d, 1J(C,F) = 3.2 Hz), 136.8 (s), 135.5 (s), 34.4 (s), 30.4 (s). 19F NMR (376 MHz, CDCl3, 25 °C, TMS): δ =
134.4 (s), 130.7 (d, 1J(C,F) = 7.7 Hz), 130.3 (s), 125.9 (s), 114.9 (d, 116.7 (s). HRMS (ESI) m/z: calcd. For C28H34FO2 [M + H] + : 421.2538,
1
J(C,F) = 21 Hz), 113.6 (s), 55.3 (s), 55.2 (s), 34.4 (s), 30.4 (s). 19F NMR found: 421.2534.
(376 MHz, CDCl3, 25 °C, TMS): δ = 117.4 (s). HRMS (ESI) m/z: calcd.
For C28H34FO2 [M + H] + : 421.2538, found: 421.2530. 4-((2-Bromophenyl)(4-methoxyphenyl)methyl)-2,6-di-tert-butylphe-
nol (3 r). According to the general procedure, work-up and flash
4-((4-Bromophenyl)(4-methoxyphenyl)methyl)-2,6-di-tert-butyl column chromatography (Rf = 0.5, Hexane/EtOAc: 20 : 1), product 3 r
phenol (3 m). According to the general procedure, work-up and (79.9 mg, 0.166 mmol, 83%) was obtained as a yellow oil. 1H NMR
flash column chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1), (400 MHz, CDCl3, 25 °C, TMS): δ = 7.53–7.55 (m, 1 H), 7.17–7.22 (m,
product 3 m (90.5 mg, 0.188 mmol, 94%) was obtained as a yellow 1 H), 6.96–7.06 (m, 4 H), 6.86 (s, 2 H), 6.80–6.82 (m, 2 H), 5.78 (s, 1 H),
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.37–7.39 (m, 2 H), 5.08 (s, 1 H), 3.77 (s, 3 H), 1.35 (s, 18 H). 13C NMR (100 MHz, CDCl3,

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25 °C, TMS): δ = 157.9 (s), 152.2 (s), 144.5 (s), 135.5 (s), 135.4 (s), 2,6-Diisopropyl-4-((4-methoxyphenyl)(phenyl)methyl) phenol (3 x).
133.3 (s), 133.0 (s), 131.2 (s), 130.5 (s), 127.7 (s), 127.1 (s), 126.3 (s), According to the general procedure, work-up and flash column
125.6 (s), 113.6 (s), 55.2 (s), 55.1 (s), 34.4 (s), 30.4 (s). HRMS (ESI) m/z: chromatography (Rf = 0.3, Hexane/EtOAc: 20 : 1), product 3 x
calcd. For C28H34BrO2 [M + H] + : 481.1737, found: 481.1732. (65.9 mg, 0.176 mmol, 88%) was obtained as a yellow oil. 1H NMR
(400 MHz, CDCl3, 25 °C, TMS): δ = 7.22–7.25 (m, 2 H), 7.15–7.19 (m,
2,6-Di-tert-butyl-4-((3-fluorophenyl)(4-methoxyphenyl) meth-
1 H), 7.09–7.11 (m, 2 H), 7.00–7.03 (m, 2 H), 6.78–6.82 (m, 4 H), 5.41
yl)phenol (3 s). According to the general procedure, work-up and (s, 1 H), 4.67 (s, 1 H), 3.77 (s, 3 H), 3.06–3.13 (m, 2 H), 1.17 (d, J =
flash column chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1), 6.8 Hz, 12 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 157.9 (s),
product 3 s (77.4 mg, 0.184 mmol, 92%) was obtained as a yellow 148.4 (s), 145.1 (s), 137.0 (s), 135.9 (s), 133.4 (s), 130.3 (s), 129.3 (s),
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.18–7.23 (m, 1 H), 128.1 (s), 126.0 (s), 124.6 (s), 113.6 (s), 55.9 (s), 55.2 (s), 27.4 (s),
7.01–7.03 (m, 2 H), 6.86–6.91 (m, 4 H), 6.81–6.83 (m, 3 H), 5.38 (s, 22.7 (s). HRMS (ESI) m/z: calcd. For C26H31O2 [M + H] + : 375.2319,
1 H), 5.10 (s, 1 H), 3.77 (s, 3 H), 1.36 (s, 18 H). 13C NMR (100 MHz, found: 375.2313.
CDCl3, 25 °C, TMS): δ = 162.9 (d, 1J(C,F) = 243.5 Hz), 158.0 (s),
152.3 (s), 148.0 (d, 1J(C,F) = 6.7 Hz), 136.3 (s), 135.6 (s), 133.9 (s), 5’-((4-Methoxyphenyl)(phenyl)methyl)-[1,1’:3’,1’’-terphenyl]-2’-ol
130.3 (s), 129.5 (d, 1J(C,F) = 8.1 Hz), 125.9 (s), 125.1 (d, 1J(C,F) = (3 y). According to the general procedure, work-up and flash
2.6 Hz), 116.3 (d, 1J(C,F) = 21.5 Hz), 113.7 (s), 112.9 (d, 1J(C,F) = column chromatography (Rf = 0.3, Hexane/EtOAc: 20 : 1), product 3 y
21 Hz), 55.8 (s), 55.3 (s), 34.4 (s), 30.4 (s). 19F NMR (376 MHz, CDCl3, (79.7 mg, 0.180 mmol, 90%) was obtained as a yellow oil. 1H NMR
25 °C, TMS): δ = 113.6 (s). HRMS (ESI) m/z: calcd. For C28H34FO2 [M (400 MHz, CDCl3, 25 °C, TMS): δ = 7.49–7.50 (m, 4 H), 7.41–7.45 (m,
+ H] + : 421.2538, found: 421.2532. 4 H), 7.32–7.36 (m, 2 H), 7.24–7.30 (m, 2 H), 7.17–7.19 (m, 3 H), 7.08–
7.10 (m, 2 H), 7.02–7.04 (m, 2 H), 6.81–6.84 (m, 2 H), 5.50 (s, 1 H),
4-((3-Bromophenyl)(4-methoxyphenyl)methyl)-2,6-di-tert-butyl 5.35 (s, 1 H), 3.77 (s, 3 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ =
phenol (3 t). According to the general procedure, work-up and flash 158.0 (s), 147.7 (s), 144.4 (s), 137.7 (s), 136.6 (s), 136.3 (s), 130.8 (s),
column chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1), product 3 t 130.3 (s), 129.4 (s), 129.3 (s), 128.8 (s), 128.5 (s), 128.3 (s), 127.6 (s),
(83.8 mg, 0.174 mmol, 87%) was obtained as a yellow oil. 1H NMR 126.3 (s), 113.7 (s), 55.5 (s), 55.3 (s). HRMS (ESI) m/z: calcd. For
(400 MHz, CDCl3, 25 °C, TMS): δ = 7.28–7.32 (m, 2 H), 7.10–7.14 (m, C32H27O2 [M + H] + : 443.2006, found: 443.2001.
1 H), 6.99–7.03 (m, 3 H), 6.87 (s, 2 H), 6.81–6.83 (m, 2 H), 5.34 (s, 1 H),
5.10 (s, 1 H), 3.78 (s, 3 H), 1.36 (s, 18 H). 13C NMR (100 MHz, CDCl3, 4,4’-(1,4-Phenylenebis((4-methoxyphenyl)methylene))bis (2,6-di-
25 °C, TMS): δ = 158.0 (s), 152.3 (s), 147.7 (s), 136.2 (s), 135.6 (s), tert-butylphenol) (3 z). According to the general procedure, work-
133.7 (s), 132.4 (s), 130.3 (s), 129.7 (s), 129.2 (s), 128.0 (s), 125.9 (s), up and flash column chromatography (Rf = 0.4, Hexane/EtOAc:
122.4 (s), 113.7 (s), 55.7 (s), 55.3 (s), 34.4 (s), 30.4 (s). HRMS (ESI) m/z: 20 : 1), product 3 z (126.5 mg, 0.174 mmol, 87%) was obtained as a
calcd. For C28H34BrO2 [M + H] + : 481.1737, found: 481.1730. yellow oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.00–7.02 (m,
8 H), 6.89 (s, 4 H), 6.78–6.80 (m, 4 H), 5.36 (s, 2 H), 5.06 (s, 2 H), 3.76
3-((3,5-Di-tert-butyl-4-hydroxyphenyl)(4-methoxyphenyl) meth- (s, 6 H), 1.35 (s, 36 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ =
yl)benzonitrile (3 u). According to the general procedure, work-up 157.8 (s), 152.0 (s), 142.8 (s), 137.3 (s), 135.4 (s), 134.8 (s), 130.4 (s),
and flash column chromatography (Rf = 0.5, Hexane/EtOAc: 20 : 1), 129.1 (s), 126.0 (s), 113.5 (s), 55.7 (s), 55.3 (s), 34.4 (s), 30.4 (s). HRMS
product 3 u (79.5 mg, 0.186 mmol, 93%) was obtained as a yellow (ESI) m/z: calcd. For C50H63O4 [M + H] + : 727.4721, found: 727.4715.
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.47–7.50 (m, 1 H),
7.36–7.38 (m, 3 H), 6.97–6.99 (m, 2 H), 6.83–6.85 (m, 4 H), 5.41 (s, 2,6-Di-tert-butyl-4-((2,3-dihydrobenzofuran-6-yl)(4-meth-
1 H), 5.13 (s, 1 H), 3.80 (s, 3 H), 1.36 (s, 18 H). 13C NMR (100 MHz, oxyphenyl)methyl)phenol (3 aa). According to the general proce-
CDCl3, 25 °C, TMS): δ = 158.2 (s), 152.4 (s), 146.9 (s), 135.9 (s), dure, work-up and flash column chromatography (Rf = 0.5, Hexane/
135.4 (s), 133.9 (s), 133.1 (s), 132.8 (s), 130.2 (s), 129.9 (s), 128.9 (s), EtOAc: 20 : 1), product 3 aa (72.0 mg, 0.162 mmol, 81% was
125.8 (s), 119.2 (s), 113.9 (s), 112.2 (s), 55.6 (s), 55.3 (s), 34.4 (s), obtained) as a yellow oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ =
30.3 (s). HRMS (ESI) m/z: calcd. For C29H34NO2 [M + H] + : 428.2585, 7.01–7.03 (m, 2 H), 6.90–6.94 (m, 3 H), 6.80–6.83 (m, 3 H), 6.66–6.68
found: 428.2579. (m, 1 H), 5.32 (s, 1 H), 5.06 (s, 1 H), 4.53 (t, J = 8.6 Hz, 2 H), 3.78 (s,
3 H), 3.13 (t, J = 8.6 Hz, 2 H), 1.36 (s, 18 H). 13C NMR (100 MHz, CDCl3,
2,6-Di-tert-butyl-4-((4-methoxyphenyl)(3-nitrophenyl) meth- 25 °C, TMS): δ = 158.3 (s), 157.7 (s), 152.0 (s), 137.6 (s), 137.4 (s),
yl)phenol (3 v). According to the general procedure, work-up and
135.4 (s), 134.9 (s), 130.2 (s), 128.8 (s), 126.7 (s), 125.9 (s), 125.8 (s)
flash column chromatography (Rf = 0.5, Hexane/EtOAc: 20 : 1),
113.5 (s), 108.7 (s), 71.2 (s), 55.5 (s), 55.2 (s), 34.4 (s), 30.4 (s), 29.9 (s).
product 3 v (83.2 mg, 0.186 mmol, 93%) was obtained as a yellow HRMS (ESI) m/z: calcd. For C30H37O3 [M + H] + : 445.2738, found:
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 8.01–8.07 (m, 2 H), 445.2734.
7.43–7.45 (m, 2 H), 6.99–7.02 (m, 2 H), 6.83–6.87 (m, 4 H), 5.48 (s,
1 H), 5.14 (s, 1 H), 3.80 (s, 1 H), 1.36 (s, 18 H). 13C NMR (100 MHz, 2,6-Di-tert-butyl-4-((3,4-dimethoxyphenyl)(phenyl)methyl) phenol
CDCl3, 25 °C, TMS): δ = 158.2 (s), 152.5 (s), 148.3 (s), 147.5 (s), (4 a). According to the general procedure, work-up and flash
135.9 (s), 135.5 (s), 135.4 (s), 133.0 (s), 130.2 (s), 129.0 (s), 125.8 (s), column chromatography (Rf = 0.5, Hexane/EtOAc: 20 : 1), product 4 a
124.1 (s), 121.3 (s), 113.9 (s), 55.7 (s), 55.3 (s), 34.4 (s), 30.3 (s). HRMS (74.4 mg, 0.172 mmol, 86%) was obtained as a yellow oil. 1H NMR
(ESI) m/z: calcd. For C28H34NO4 [M + H] + : 448.2483, found: 448.2475. (400 MHz, CDCl3, 25 °C, TMS): δ = 7.24–7.28 (m, 2 H), 7.16–7.19 (m,
1 H), 7.10–7.12 (m, 2 H), 6.92 (s, 2 H), 6.77–6.79 (m, 1 H), 6.67–6.69
4-((4-Methoxyphenyl)(phenyl)methyl)-2,6-dimethylphenol (3 w). Ac-
(m, 1 H), 6.60–6.63 (m, 1 H), 5.38 (s, 1 H), 5.07 (s, 1 H), 3.85 (s, 3 H),
cording to the general procedure, work-up and flash column 3.76 (s, 3 H), 1.36 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS):
chromatography (Rf = 0.3, Hexane/EtOAc: 20 : 1), product 3 w δ = 152.1 (s), 148.6 (s), 147.3 (s), 145.1 (s), 137.5 (s), 135.5 (s),
(52.2 mg, 0.164 mmol, 82%) as a yellow oil. 1H NMR (400 MHz, 134.3 (s), 129.3 (s), 128.1 (s), 126.0 (s), 126.0 (s), 121.5 (s), 112.9 (s),
CDCl3, 25 °C, TMS): δ = 7.25–7.29 (m, 2 H), 7.17–7.21 (m, 1 H), 7.09– 110.8 (s), 56.4 (s), 55.9 (s), 55.8 (s), 34.4 (s), 30.4 (s). HRMS (ESI) m/z:
7.11 (m, 2 H), 7.00–7.03 (m, 2 H), 6.80–6.83 (m, 2 H), 6.71 (s, 2 H), calcd. For C29H37O3 [M + H] + : 433.2738, found: 433.2733.
5.37 (s, 1 H), 4.51 (s, 1 H), 3.78 (s, 3 H), 2.17 (s, 6 H). 13C NMR
(100 MHz, CDCl3, 25 °C, TMS): δ = 157.9 (s), 150.5 (s), 144.7 (s), 2,6-Di-tert-butyl-4-((3-(tert-butyl)-4-methoxyphenyl)(phenyl) meth-
136.6 (s), 135.8 (s), 130.3 (s), 129.5 (s), 129.3 (s), 128.2 (s), 126.0 (s), yl)phenol (4 b). According to the general procedure, work-up and
122.7 (s), 113.6 (s), 55.3 (s), 55.2 (s), 16.0 (s). HRMS (ESI) m/z: calcd. flash column chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1),
For C22H23O2 [M + H] + : 319.1693, found: 319.1689. product 4 b (73.4 mg, 0.160 mmol, 80%) was obtained as a yellow

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oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.23–7.27 (m, 2 H), (m, 2 H), 5.75 (s, 1 H), 5.02 (s, 1 H), 3.69 (s, 3 H), 2.84–2.90 (m, 1 H),
7.10–7.18 (m, 3 H), 7.04–7.05 (m, 1 H), 6.88–6.93 (m, 3 H), 6.76–6.78 1.35 (s, 18 H), 1.24 (d, J = 6.8 Hz, 6 H). 13C NMR (100 MHz, CDCl3,
(m, 1 H), 5.36 (s, 1 H), 5.05 (s, 1 H), 3.80 (s, 3 H), 1.36 (s, 18 H), 1.29 (s, 25 °C, TMS): δ = 157.0 (s), 151.9 (s), 148.1 (s), 145.1 (s), 135.2 (s),
9 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 156.8 (s), 152.0 (s), 134.3 (s), 130.9 (s), 130.0 (s), 129.3 (s), 127.8 (s), 126.3 (s), 125.6 (s),
145.6 (s), 137.6(s), 136.1 (s), 135.3 (s), 134.7 (s), 129.3 (s), 128.0 (s), 118. 0 (s), 109.2 (s), 55.6 (s), 49.4 (s), 34.4 (s), 34.1 (s), 30.4 (s), 24.1 (s).
127.9 (s), 127.6 (s), 126.0 (s), 125.8 (s), 111.1 (s), 56.4 (s), 55.0 (s), HRMS (ESI) m/z: calcd. For C31H41O2 [M + H] + : 445.3102, found:
34.8 (s), 34.4 (s), 30.4 (s), 29.8 (s). HRMS (ESI) m/z: calcd. For C32H43O2 445.3095.
[M + H] + : 459.3258, found: 459.3250.
2,6-Di-tert-butyl-4-((3,5-diisopropyl-4-methoxyphenyl)
2,6-Di-tert-butyl-4-((3-isopropyl-4-methoxyphenyl)(phenyl) meth- (phenyl)methyl)phenol (4 h). According to the general procedure,
yl)phenol (4 c). According to the general procedure, work-up and work-up and flash column chromatography (Rf = 0.4, Hexane/EtOAc:
flash column chromatography (Rf = 0.5, Hexane/EtOAc: 20 : 1), 10 : 1), product 4 h (84.7 mg, 0.174 mmol, 87%) was obtained as a
product 4 c (81.8 mg, 0.184 mmol, 92%) was obtained as a yellow yellow oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.24–7.26 (m,
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.01–7.17 (m, 5 H), 2 H), 7.15–7.19 (m, 1 H), 7.11–7.13 (m, 2 H), 6.89–6.93 (m, 2 H), 6.82
6.75–6.89 (m, 4 H), 6.61–6.64 (m, 1 H), 5.28 (s, 1 H), 4.96 (s, 1 H), 3.67 (s, 2 H), 5.35 (s, 1 H), 5.05 (s, 1 H), 3.71 (s, 3 H), 3.24–3.33 (m, 2 H),
(s, 3 H), 3.15–3.22 (m, 1 H), 1.27 (s, 18 H), 1.02–1.04 (m, 6 H). 1.35 (s, 18 H), 1.13 (d, J = 6.8 Hz, 12 H). 13C NMR (100 MHz, CDCl3,
13
C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 155.1 (s), 152.1 (s), 25 °C, TMS): δ = 152.6 (s), 152.0 (s), 145.5 (s), 140.9 (s), 140.2 (s),
145.6 (s), 136.7 (s), 136.5 (s), 135.4 (s), 134.8 (s), 129.4 (s), 128.1 (s), 135.3 (s), 134.7 (s), 129.3 (s), 128.0 (s), 126.0 (s), 125.8 (s), 125.2 (s),
127.3 (s), 127.3 (s), 126.1 (s), 125.9 (s), 110.0 (s), 56.4 (s), 55.4 (s), 62.2 (s), 56.7 (s), 34.3 (s), 30.3 (s), 26.5 (s), 24.0 (s). HRMS (ESI) m/z:
34.4 (s), 30.5 (s), 26.9 (s), 22.8 (s). HRMS (ESI) m/z: calcd. For C31H41O2 calcd. For C34H47O2 [M + H] + : 487.3571, found: 487.3563.
[M + H] + : 445.3102, found: 445.3097.
2,6-Di-tert-butyl-4-((4-methoxy-3,5-dimethylphenyl)(phenyl) meth-
2,6-Di-tert-butyl-4-((3-ethyl-4-methoxyphenyl)(phenyl) meth- yl)phenol (4 i). According to the general procedure, work-up and
yl)phenol (4 d). According to the general procedure, work-up and flash column chromatography (Rf = 0.5, Hexane/EtOAc: 10 : 1),
flash column chromatography (Rf = 0.5, Hexane/EtOAc: 20 : 1), product 4 i (62.0 mg, 0.144 mmol, 72%) was obtained as a yellow
product 4 d (78.4 mg, 0.182 mmol, 91%) was obtained as a yellow oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.24–7.28 (m, 2 H),
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.23–7.26 (m, 2 H), 7.10–7.19 (m, 3 H), 6.91 (s, 2 H), 6.76 (s, 2 H), 5.30 (s, 1 H), 5.06 (s,
7.10–7.17 (m, 3 H), 6.92–6.93 (m, 3 H), 6.85–6.87 (m, 1 H), 6.71–6.73 1 H), 3.69 (s, 3 H), 2.21 (s, 6 H), 1.36 (s, 18 H). 13C NMR (100 MHz,
(m, 1 H), 5.36 (s, 1 H), 5.05 (s, 1 H), 3.77 (s, 3 H), 2.51–2.62 (m, 1 H), CDCl3, 25 °C, TMS): δ = 155.2 (s), 152.0 (s), 145.2 (s), 139.9 (s),
1.35 (s, 18 H), 1.12 (t, J = 7.6 Hz, 3 H). 13C NMR (100 MHz, CDCl3, 135.4 (s), 134.3 (s), 130.2 (s), 129.7 (s), 129.3 (s), 128.1 (s), 126.0 (s),
25 °C, TMS): δ = 155.7 (s), 152.0 (s), 145.5 (s), 136.7 (s), 135.4 (s), 125.9 (s), 59.7 (s), 56.3 (s), 34.4 (s), 30.4 (s), 16.2 (s). HRMS (ESI) m/z:
134.7 (s), 132.2 (s), 130.2 (s), 129.4 (s), 128.1 (s), 127.5 (s), 126.1 (s), calcd. For C30H39O2 [M + H] + : 431.2945, found: 431.2939.
125.9 (s), 109.8 (s), 56.2 (s), 55.4 (s), 34.4 (s), 30.4 (s), 23.4 (s), 14.4 (s).
HRMS (ESI) m/z: calcd. For C30H39O2 [M + H] + : 431.2945, found: 2,6-Di-tert-butyl-4-(phenyl(2,3,4-trimethoxyphenyl)methyl) phenol
431.2938. (4 j). According to the general procedure, work-up and flash column
chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1), product 4 j
2,6-Di-tert-butyl-4-((4-methoxy-3-methylphenyl)(phenyl) methyl (81.4 mg, 0.176 mmol, 88%) was obtained as a yellow oil. 1H NMR
phenol (4 e). According to the general procedure, work-up and flash (400 MHz, CDCl3, 25 °C, TMS): δ = 7.24–7.28 (m, 2 H), 7.11–7.18 (m,
column chromatography (Rf = 0.5, Hexane/EtOAc: 20 : 1), product 4 e 3 H), 6.90 (s, 2 H), 6.52–6.58 (m, 2 H), 5.71 (s, 1 H), 5.05 (s, 1 H), 3.86
(78.3 mg, 0.188 mmol, 94%) was obtained as a yellow oil. 1H NMR (s, 3 H), 3.83 (s, 3 H), 3.42 (s, 3 H), 1.35 (s, 18 H). 13C NMR (100 MHz,
(400 MHz, CDCl3, 25 °C, TMS): δ = 7.23–7.26 (m, 2 H), 7.10–7.17 (m, CDCl3, 25 °C, TMS): δ = 152.1 (s), 152.0 (s), 151.7 (s), 144.8 (s),
3 H), 6.91–6.93 (m, 3 H), 6.84–6.86 (m, 1 H), 6.70–6.72 (m, 1 H), 5.35 142.3 (s), 135.4 (s), 134.2 (s), 131.7 (s), 129.4 (s), 128.0 (s), 126.1 (s),
(s, 1 H), 5.05 (s, 1 H), 3.78 (s, 3 H), 2.15 (s, 3 H), 1.36 (s, 18 H). 125.9 (s), 124.2 (s), 106.5 (s), 60.7 (s), 60.4 (s), 55.9 (s), 50.1 (s),
13
C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 156.1 (s), 152.0 (s), 34.4 (s), 30.4 (s). HRMS (ESI) m/z: calcd. For C30H39O4 [M + H] + :
145.4 (s), 136.6 (s), 135.4 (s), 134.6 (s), 131.8 (s), 129.4 (s), 128.1 (s), 463.2843, found: 463.2839.
127.4 (s), 126.1 (s), 126.0 (s), 125.9 (s), 109.5 (s), 56.2 (s), 55.3 (s),
4-Allyl-5-((3,5-di-tert-butyl-4-hydroxyphenyl)(phenyl) methyl)-2-
34.4 (s), 30.4 (s), 16.4 (s). HRMS (ESI) m/z: calcd. For C29H37O2 [M +
methoxyphenol (4 k). According to the general procedure, work-up
H] + : 417.2789, found: 417.2782.
and flash column chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1),
2,6-Di-tert-butyl-4-((2,4-dimethoxyphenyl)(phenyl)methyl) phenol product 4 k (76.1 mg, 0.166 mmol, 83%) was obtained as a yellow
(4 f). According to the general procedure, work-up and flash column oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): 7.22–7.26(m, 2 H), 7.14–
chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1), product 4 f 7.18 (m, 1 H), 7.05–7.07 (m, 2 H), 6.80 (s, 2 H), 6.65 (s, 1 H), 6.49 (s,
(80.5 mg, 0.186 mmol, 93%) was obtained as a yellow oil. 1H NMR 1 H), 5.84–5.93 (m, 1 H), 5.54 (s, 1 H), 5.41 (s, 1 H), 5.04–5.06 (m, 2 H),
(400 MHz, CDCl3, 25 °C, TMS): δ = 7.21–7.25 (m, 2 H), 7.13–7.16 (m, 4.96–5.00 (m, 1 H), 3.85 (s, 3 H), 3.17–3.31 (m, 2 H), 1.34 (s, 18 H).
13
1 H), 7.06–7.08 (m, 2 H), 6.87 (s, 2 H), 6.75–6.77 (m, 1 H), 6.44–6.45 C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 152.0 (s), 144.7 (s),
(m, 1 H), 6.38–6.41 (m, 1 H), 5.71 (s, 1 H), 5.03 (s, 1 H), 3.78 (s, 3 H), 144.3 (s), 143.4 (s), 137.8 (s), 136.2 (s), 135.4 (s), 134.2 (s), 129.5 (s),
3.69 (s, 3 H), 1.35 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): 129.5 (s), 128.1 (s), 126.1 (s), 125.9 (s), 116.4 (s), 115.4 (s), 112.3 (s),
δ = 159.2 (s), 158.0 (s), 151.8 (s), 145.1 (s), 135.2 (s), 134.3 (s), 55.9 (s), 52.0 (s), 37.0 (s), 34.3 (s), 30.4 (s). HRMS (ESI) m/z: calcd. For
130.6 (s), 129.2 (s), 127.8 (s), 126.2 (s), 126.2 (s), 125.6 (s), 103.7 (s), C31H39O3 [M + H] + : 459.2894, found: 459.2888.
98.6 (s), 55.6 (s), 55.3 (s), 49.0 (s), 34.3 (s), 30.4 (s). HRMS (ESI) m/z:
calcd. For C29H37O3 [M + H] + : 433.2738, found: 433.2733. 4-((2-Allyl-4,5-dimethoxyphenyl)(phenyl)methyl)-2,6-di-tert-butyl-
phenol (4 l). According to the general procedure, work-up and flash
2,6-Di-tert-butyl-4-((2-isopropyl-4-methoxyphenyl)(phenyl) meth- column chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1), product 4 l
yl)phenol (4 g). According to the general procedure, work-up and (82.2 mg, 0.174 mmol, 87%) was obtained as a yellow oil. 1H NMR
flash column chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1), (400 MHz, CDCl3, 25 °C, TMS): δ = 7.23–7.27 (m, 2 H), 7.15–7.19 (m,
product 4 g (80.0 mg, 0.180 mmol, 90%) was obtained as a yellow 1 H), 7.05–7.07 (m, 2 H), 6.85 (s, 2 H), 6.68 (s, 1 H), 6.42 (s, 1 H), 5.84–
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.20–7.24 (m, 2 H), 5.94 (m, 1 H), 5.57 (s, 1 H), 5.05 (s, 1 H), 4.96–5.03 (m, 2 H), 3.85 (s,
7.08–7.15 (m, 3 H), 6.89–6.93 (m, 2 H), 6.78–6.81 (m, 1 H), 6.71–6.73 3 H), 3.61 (s, 3 H), 3.20–3.32 (m, 2 H), 1.35 (s, 18 H). 13C NMR

Chem Asian J. 2023, 18, e202201156 (10 of 15) © 2022 Wiley-VCH GmbH
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Research Article
(100 MHz, CDCl3, 25 °C, TMS): δ = 152.0 (s), 147.1 (s), 146.9 (s), 6.0 Hz), 129.1 (s), 128.1 (s), 126.1 (s), 125.9 (s), 124.9 (d, 1J(C,F) =
144.5 (s), 137.6 (s), 135.5 (s), 135.2 (s), 134.2 (s), 130.2 (s), 129.3 (s), 15.0 Hz), 109.4 (d, 1J(C,F) = 3.1 Hz), 101.5 (d, 1J(C,F) = 25.9 Hz),
128.1 (s), 126.0 (s), 125.9 (s), 115.4 (s), 113.7 (s), 113.1 (s), 55.9 (s), 55.5 (s), 48.7 (s), 34.4 (s), 30.3 (s). 19F NMR (376 MHz, CDCl3, 25 °C,
55.7 (s), 52.1 (s), 36.9 (s), 34.3 (s), 30.3 (s). HRMS (ESI) m/z: calcd. For TMS): δ = 114.4 (s). HRMS (ESI) m/z: calcd. For C28H34FO2 [M + H] + :
C32H41O3 [M + H] + : 473.3051, found: 473.3044. 421.2538, found: 421.2531.
4-((2-Bromo-4,5-dimethoxyphenyl)(phenyl)methyl)-2,6-di-tert-butyl 2,6-Di-tert-butyl-4-((2-chloro-4-methoxyphenyl)(phenyl) meth-
phenol (4 m). According to the general procedure, work-up and yl)phenol (4 r). According to the general procedure, work-up and
flash column chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1), flash column chromatography (Rf = 0.5, Hexane/EtOAc: 20 : 1),
product 4 m (74.7 mg, 0.146 mmol, 73%) was obtained as a yellow product 4 r (71.7 mg, 0.164 mmol, 82%) was obtained as a yellow
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.25–7.29 (m, 2 H), oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.24–7.28 (m, 2 H),
7.17–7.21 (m, 1 H), 7.07–7.09 (m, 2 H), 7.03 (s, 1 H), 6.89 (s, 2 H), 6.49 7.16–7.20 (m, 1 H), 7.06–7.08 (m, 2 H), 6.92–6.93 (m, 1 H), 6.85–6.87
(s, 1 H), 5.75 (s, 1 H), 5.09 (s, 1 H), 3.85 (s, 3 H), 3.63 (s, 3 H), 1.36 (s, (m, 3 H), 6.71–6.73 (m, 1 H), 5.78 (s, 1 H), 5.07 (s, 1 H), 3.77 (s, 3 H),
18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 152.2 (s), 148.0 (s), 1.35 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 158.4 (s),
147.9 (s), 143.6 (s), 136.1 (s), 135.6 (s), 133.3 (s), 129.3 (s), 128.2 (s), 152.1 (s), 143.7 (s), 135.5 (s), 134.8 (s), 134.7 (s), 133.3 (s), 131.5 (s),
126.2 (s), 126.1 (s), 115.5 (s), 115.3 (s), 114.0 (s), 56.1 (s), 55.8 (s), 129.4 (s), 128.1 (s), 126.2 (s), 126.1 (s), 114.7 (s), 112.6 (s), 55.5 (s),
55.4 (s), 34.4 (s), 30.4 (s). HRMS (ESI) m/z: calcd. For C29H36BrO3 [M + 52.6 (s), 34.4 (s), 30.4 (s). HRMS (ESI) m/z: calcd. For C28H34ClO2 [M +
H] + : 511.1843, found: 511.1835. H] + : 437.2242, found: 437.2237.
2,6-Di-tert-butyl-4-((3-fluoro-4-methoxyphenyl)(phenyl) meth- 4-((2-Bromo-4-methoxyphenyl)(phenyl)methyl)-2,6-di-tert-butylphe-
yl)phenol (4 n). According to the general procedure, work-up and nol (4 s). According to the general procedure, work-up and flash
flash column chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1), column chromatography (Rf = 0.5, Hexane/EtOAc: 20 : 1), product 4 s
product 4 n (63.9 mg, 0.152 mmol, 76%) was obtained as a yellow (80.9 mg, 0.168 mmol, 84%) was obtained as a yellow oil. 1H NMR
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.25–7.29 (m, 2 H), (400 MHz, CDCl3, 25 °C, TMS): δ = 7.24–7.28 (m, 2 H), 7.16–7.20 (m,
7.17–7.21 (m, 1 H), 7.09–7.10 (m, 2 H), 6.79–6.88 (m, 5 H), 5.36 (s, 1 H), 7.11–7.12 (m, 1 H), 7.06–7.07 (m, 2 H), 6.85–6.87 (m, 3 H), 6.75–
1 H), 5.09 (s, 1 H), 3.86 (s, 3 H), 1.36 (s, 18 H). 13C NMR (100 MHz, 6.78 (m, 1 H), 5.76 (s, 1 H), 5.07 (s, 1 H), 3.77 (s, 3 H), 1.35 (s, 18 H).
CDCl3, 25 °C, TMS): δ = 152.2 (d, 1J(C,F) = 243.6 Hz), 152.2 (s), 145.8 13
C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 158.3 (s), 152.1 (s),
(d, 1J(C,F) = 10.7 Hz), 144.4 (s), 138.2 (d, 1J(C,F) = 5.4 Hz), 135.6 (s), 143.7 (s), 136.3 (s), 135.5 (s), 133.4 (s), 131.5 (s), 129.5 (s), 128.1 (s),
133.9 (s), 129.3 (s), 128.2 (s), 126.2 (s), 125.9 (s), 124.9 (d, 1J(C,F) = 126.2 (s), 126.1 (s), 125.5 (s), 118.0 (s), 113.3 (s), 55.5 (s), 55.1 (s),
3.3 Hz), 117.1 (d, 1J(C,F) = 18.5 Hz), 113.0 (s), 56.3 (s), 55.9 (s), 34.4 (s), 34.4 (s), 30.4 (s). HRMS (ESI) m/z: calcd. For C28H34BrO2 [M + H] + :
30.3 (s). 19F NMR (376 MHz, CDCl3, 25 °C, TMS): δ = 135.6 (s). HRMS 481.1737, found: 481.1731.
(ESI) m/z: calcd. For C28H34FO2 [M + H] + : 421.2538, found: 421.2532.
2,6-Di-tert-butyl-4-((2-iodo-4-methoxyphenyl)(phenyl) meth-
2,6-Di-tert-butyl-4-((3-chloro-4-methoxyphenyl)(phenyl) meth- yl)phenol (4 t). According to the general procedure, work-up and
yl)phenol (4 o). According to the general procedure, work-up and flash column chromatography (Rf = 0.5, Hexane/EtOAc: 20 : 1),
flash column chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1), product 4 t (94.1 mg, 0.178 mmol, 89%) was obtained as a yellow
product 4 o (69.0 mg, 0.158 mmol, 79%) was obtained as a yellow oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.39–7.40 (m, 1 H),
solid. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.28–7.29 (m, 2 H), 7.24–7.28 (m, 2 H), 7.19–7.20 (m, 1 H), 7.05–7.07 (m, 2 H), 6.82–6.85
7.20–7.21 (m, 1 H), 7.14–7.15 (m, 1 H), 7.08–7.10 (m, 2 H), 6.93–6.95 (m, 4 H), 5.64 (m, 1 H), 5.07 (s, 1 H), 3.76 (s, 3 H), 1.35 (s, 18 H).
13
(m, 1 H), 6.88 (s, 2 H), 6.82–6.84 (m, 1 H), 5.35 (s, 1 H), 5.09 (s, 1 H), C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 158.1 (s), 152.1 (s),
3.87 (s, 3 H), 1.36 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): 143.7 (s), 139.5 (s), 135.5 (s), 133.6 (s), 130.7 (s), 129.7 (s), 128.1 (s),
δ = 153.2 (s), 152.2 (s), 144.4 (s), 138.2 (s), 135.6 (s), 133.8 (s), 126.3 (s), 126.1 (s), 124.6 (s), 114.1 (s), 102.3 (s), 59.7 (s), 55.5 (s),
131.1 (s), 129.3 (s), 128.5 (s), 128.2 (s), 126.2 (s), 125.9 (s), 122.0 (s), 34.4 (s), 30.4 (s). HRMS (ESI) m/z: calcd. For C28H34IO2 [M + H] + :
111.7 (s), 56.2 (s), 55.8 (s), 34.4 (s), 30.3 (s). HRMS (ESI) m/z: calcd. For 529.1598, found: 529.1593.
C28H34ClO2 [M + H] + : 437.2242, found: 437.2238.
2,6-Di-tert-butyl-4-((6-methoxy-[1,1’-biphenyl]-3-yl)(phenyl) meth-
4-((3-Bromo-4-methoxyphenyl)(phenyl)methyl)-2,6-di-tert-butylphe- yl)phenol (4 u). According to the general procedure, work-up and
nol (4 p). According to the general procedure, work-up and flash flash column chromatography (Rf = 0.5, Hexane/EtOAc: 20 : 1),
column chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1), product 4 p product 4 u (89.0 mg, 0.186 mmol, 93%) was obtained as a yellow
(69.3 mg, 0.144 mmol, 72%) was obtained as a yellow oil. 1H NMR oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.46–7.48 (m, 2 H),
(400 MHz, CDCl3, 25 °C, TMS): δ = 7.32–7.33 (m, 1 H), 7.25–7.29 (m, 7.34–7.38 (m, 2 H), 7.24–7.29 (m, 3 H), 7.11–7.19 (m, 4 H), 7.01–7.04
2 H), 7.17–7.21 (m, 1 H), 7.08–7.10 (m, 2 H), 6.97–6.99 (m, 1 H), 6.88 (m, 1 H), 6.94 (s, 2 H), 6.87–6.89 (m, 1 H), 5.42 (s, 1 H), 5.07 (s, 1 H),
(s, 2 H), 6.79–6.81 (m, 1 H), 5.35 (s, 1 H), 5.09 (s, 1 H), 3.86 (s, 3 H), 3.78 (s, 3 H), 1.36 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS):
1.36 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 154.1 (s), δ = 154.8 (s), 152.1 (s), 145.1 (s), 138.7 (s), 137.2 (s), 135.4 (s),
152.2 (s), 144.4 (s), 138.7 (s), 135.6 (s), 134.1 (s), 133.8 (s), 132.0 (s), 134.4 (s), 132.0 (s), 130.2 (s), 129.6 (s), 129.3 (s), 129.3 (s), 128.1 (s),
129.3 (s), 128.3 (s), 126.2 (s), 125.9 (s), 111.6 (s), 111.4 (s), 56.2 (s), 127.9 (s), 126.8 (s), 126.0 (s), 125.9 (s), 110.9 (s), 56.1 (s), 55.6 (s),
55.7 (s), 34.4 (s), 30.3 (s). HRMS (ESI) m/z: calcd. For C28H34BrO2 [M + 34.4 (s), 30.4 (s). HRMS (ESI) m/z: calcd. For C34H39O2 [M + H] + :
H] + : 481.1737, found: 481.1732. 479.2945, found: 479.2937.
2,6-Di-tert-butyl-4-((2-fluoro-4-methoxyphenyl)(phenyl) meth- 5-((3,5-Di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl)-2-methoxy
yl)phenol (4 q). According to the general procedure, work-up and benzaldehyde (4 v). According to the general procedure, work-up
flash column chromatography (Rf = 0.5, Hexane/EtOAc: 20 : 1), and flash column chromatography (Rf = 0.5, Hexane/EtOAc: 20 : 1),
product 4 q (68.1 mg, 0.162 mmol, 81%) was obtained as a yellow product 4 v (59.4 mg, 0.138 mmol, 69%) was obtained as a yellow
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.16–7.28 (m, 3 H), oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 10.42 (s, 1 H), 7.64–
7.05–7.10 (m, 2 H), 6.78–6.89 (m, 3 H), 6.51–6.61 (m, 2 H), 5.65 (s, 7.65 (m, 1 H), 7.26–7.31 (m, 3 H), 7.17–7.21 (m, 1 H), 7.08–7.09 (m,
1 H), 5.07 (s, 1 H), 3.77 (s, 3 H), 1.36 (s, 18 H). 13C NMR (100 MHz, 2 H), 6.87–6.92 (m, 3 H), 5.41 (s, 1 H), 5.09 (s, 1 H), 3.91 (s, 3 H), 1.35
CDCl3, 25 °C, TMS): δ = 161.1 (d, 1J(C,F) = 244.7 Hz), 159.3 (d, 1J(C,F) = (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 190.0 (s),
10.8 Hz), 152.2 (s), 143.9 (s), 135.5 (s), 133.1 (s), 131.1 (d, 1J(C,F) = 160.3 (s), 152.2 (s), 144.2 (s), 137.4 (s), 136.7 (s), 135.6 (s), 133.7 (s),

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Research Article
129.3 (s), 129.2 (s), 128.3 (s), 126.2 (s), 125.9 (s), 124.4 (s), 111.5 (s), 56.1 (s), 55.9 (s), 34.4 (s), 30.4 (s). HRMS (ESI) m/z: calcd. For C30H35O2
55.9 (s), 55.7 (s), 34.4 (s), 30.3 (s). HRMS (ESI) m/z: calcd. For C29H35O3 [M + H] + : 427.2632, found: 427.2627.
[M + H] + : 431.2581, found: 431.2575.
2,6-Di-tert-butyl-4-((4-phenoxyphenyl)(phenyl)methyl) phenol
2,6-Di-tert-butyl-4-((4-ethoxyphenyl)(phenyl)methyl)phenol (4 w). (4 ab). According to the general procedure, work-up and flash
According to the general procedure, work-up and flash column column chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1), product
chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1), product 4 w 4 ab (79.9 mg, 0.172 mmol, 86%) was obtained as a yellow oil.
(76.7 mg, 0.184 mmol, 92%) was obtained as a yellow oil. 1H NMR 1
H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.29–7.33 (m, 3 H), 7.26–
(400 MHz, CDCl3, 25 °C, TMS): δ = 7.24–7.27 (m, 2 H), 7.15–7.19 (m, 7.27 (m, 1 H), 7.18–7.22 (m, 1 H), 7.12–7.14 (m, 2 H), 7.05–7.08 (m,
1 H), 7.10–7.12 (m, 2 H), 7.00–7.02 (m, 2 H), 6.90 (s, 2 H), 6.79–6.81 3 H), 6.98–7.00 (m, 2 H), 6.90–6.93 (m, 4 H), 5.43 (s, 1 H), 5.09 (s, 1 H),
(m, 2 H), 5.39 (s, 1 H), 5.07 (s, 1 H), 3.97-4.02 (m, 2 H), 1.35–1.41 (m, 1.36 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 157.5 (s),
3 H), 1.35 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 155.2 (s), 152.1 (s), 144.8 (s), 139.9 (s), 135.5 (s), 134.2 (s), 130.6 (s),
157.2 (s), 152.0 (s), 145.2 (s), 137.0 (s), 135.4 (s), 134.5 (s), 130.3 (s), 129.7 (s), 129.4 (s), 128.2 (s), 126.1 (s), 126.0 (s), 123.0 (s), 118.8 (s),
129.4 (s), 128.1 (s), 126.0 (s), 126.0 (s), 114.1 (s), 63.4 (s), 56.0 (s), 118.6 (s), 56.1 (s), 34.4 (s), 30.3 (s). HRMS (ESI) m/z: calcd. For
34.4 (s), 30.4 (s), 15.0 (s). HRMS (ESI) m/z: calcd. For C29H37O2 [M + C33H37O2 [M + H] + : 465.2789, found: 465.2782.
H] + : 417.2789, found: 417.2785.
2,6-Di-tert-butyl-4-((4-hydroxyphenyl)(phenyl)methyl) phenol (6 a).
2,6-Di-tert-butyl-4-(phenyl(4-propoxyphenyl)methyl)phenol (4 x). According to the general procedure, work-up and flash column
According to the general procedure, work-up and flash column chromatography (Rf = 0.4, Hexane/EtOAc: 10 : 1), product 6 a (4 h,
chromatography (Rf = 0.5, Hexane/EtOAc: 20 : 1), product 4 x 69.9 mg, 0.180 mmol, 90%) was obtained as a colorless oil.[14c]
(80.9 mg, 0.188 mmol, 94%) was obtained as a yellow oil. 1H NMR 1
H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.24–7.28 (m, 2 H), 7.16–
(400 MHz, CDCl3, 25 °C, TMS): δ = 7.23–7.27 (m, 2 H), 7.15–7.19 (m, 7.19 (m, 1 H), 7.09–7.11 (m, 2 H), 6.96–6.98 (m, 2 H), 6.89 (s, 2 H),
1 H), 7.10–7.12 (m, 2 H), 7.00–7.02 (m, 2 H), 6.90 (s, 2 H), 6.79–6.81 6.72–6.74 (m, 2 H), 5.37 (s, 1 H), 5.06 (s, 1 H), 4.70 (s, 1 H), 1.35 (s,
(m, 2 H), 5.38 (s, 1 H), 5.07 (s, 1 H), 3.89 (t, J = 6.6 Hz, 2 H), 1.74–1.83 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 153.7 (s), 152.0 (s),
(m, 2 H), 1.36 (s, 18 H), 1.02 (t, J = 7.4 Hz, 3 H). 13C NMR (100 MHz, 145.1 (s), 137.3 (s), 135.4 (s), 134.4 (s), 130.6 (s), 130.5 (s), 129.3 (s),
CDCl3, 25 °C, TMS): δ = 157.4 (s), 152.0 (s), 145.3 (s), 136.9 (s), 128.1 (s), 126.0 (s), 114.9 (s), 56.0 (s), 34.3 (s), 30.3 (s).
135.4 (s), 134.5 (s), 130.3 (s), 129.4 (s), 128.1 (s), 126.0 (s), 125.9 (s),
114.1 (s), 69.5 (s), 56.0 (s), 34.4 (s), 30.4 (s), 22.7 (s), 10.6 (s). HRMS 2,6-Di-tert-butyl-4-((4-hydroxy-3-methylphenyl)(phenyl) meth-
(ESI) m/z: calcd. For C30H39O2 [M + H] + : 431.2945, found: 431.2940. yl)phenol (6 b). According to the general procedure, work-up and
flash column chromatography (Rf = 0.4, Hexane/EtOAc: 10 : 1),
4-((4-(Benzyloxy)phenyl)(phenyl)methyl)-2,6-di-tert-butyl phenol product 6 b (4 h, 71.7 mg, 0.178 mmol, 89%) was obtained as a
(4 y). According to the general procedure, work-up and flash colorless oil.[14c] 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.24–7.27
column chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1), product 4 y (m, 2 H), 7.15–7.19 (m, 1 H), 7.09–7.11 (m, 2 H), 6.90 (s, 3 H), 6.76–
(82.3 mg, 0.172 mmol, 86%) was obtained as a yellow oil. 1H NMR 6.79 (m, 1 H), 6.65–6.67 (m, 1 H), 5.34 (s, 1 H), 5.06 (s, 1 H), 4.60 (s,
(400 MHz, CDCl3, 25 °C, TMS): δ = 7.40–7.42 (m, 2 H), 7.34–7.37 (m, 1 H), 2.18 (s, 3 H), 1.36 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C,
2 H), 7.23–7.31 (m, 3 H), 7.17–7.18 (m, 1 H), 7.10–7.12 (m, 2 H), 7.01– TMS): δ = 152.0 (s), 152.0 (s), 145.3 (s), 137.1 (s), 135.4 (s), 134.5 (s),
7.03 (m, 2 H), 6.87–6.89 (m, 4 H), 5.39 (s, 1 H), 5.06 (s, 1 H), 5.02 (s, 132.1 (s), 129.3 (s), 128.1 (s), 127.9 (s), 126.0 (s), 125.9 (s), 123.3 (s),
2 H), 1.35 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 114.6 (s), 56.1 (s), 34.4 (s), 30.4 (s), 15.9 (s).
157.1 (s), 152.1 (s), 145.2 (s), 137.4 (s), 137.2 (s), 135.5 (s), 134.5 (s),
130.4 (s), 129.4 (s), 128.6 (s), 128.2 (s), 127.9 (s), 127.6 (s), 126.0 (s), 4-((3-Bromo-4-hydroxyphenyl)(phenyl)methyl)-2,6-di-tert-butyl
126.0 (s), 114.5 (s), 70.1 (s), 56.1 (s), 34.4 (s), 30.4 (s). HRMS (ESI) m/z: phenol (6 c). According to the general procedure, work-up and flash
calcd. For C34H39O2 [M + H] + : 479.2945, found: 479.2939. column chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1), product 6 c
(4 h, 74.8 mg, 0.160 mmol, 80%) was obtained as a colorless oil.
1
4-((4-(Allyloxy)phenyl)(phenyl)methyl)-2,6-di-tert-butyl phenol (4 z). H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.24–7.29 (m, 2 H), 7.18–
According to the general procedure, work-up and flash column 7.22 (m, 2 H), 7.08–7.10 (m, 2 H), 6.91–6.96 (m, 2 H), 6.87 (s, 2 H),
chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1), product 4 z 5.41 (s, 1 H), 5.35 (s, 1 H), 5.09 (s, 1 H), 1.36 (s, 18 H). 13C NMR
(66.9 mg, 0.156 mmol, 78%) was obtained as a yellow oil. 1H NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 152.3 (s), 150.4 (s), 144.4 (s),
(400 MHz, CDCl3, 25 °C, TMS): δ = 7.24–7.28 (m, 2 H), 7.15–7.19 (m, 138.8 (s), 135.6 (s), 133.7 (s), 132.6 (s), 130.2 (s), 129.3 (s), 128.3 (s),
1 H), 7.09–7.11 (m, 2 H), 7.00–7.02 (m, 2 H), 6.89 (s, 2 H), 6.81–6.83 126.3 (s), 125.9 (s), 115.6 (s), 110.0 (s), 55.7 (s), 34.4 (s), 30.3 (s). HRMS
(m, 2 H), 6.00–6.10 (m, 1 H), 5.40 (d, J = 6.8 Hz, 2 H), 5.26 (d, J = (ESI) m/z: calcd. For C27H32BrO2 [M + H] + : 467.1581, found: 467.1574.
5.2 Hz, 1 H), 5.06 (s, 1 H), 4.50 (d, J = 2.6 Hz, 2 H), 1.35 (s, 18 H).
13
C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 156.9 (s), 152.0 (s), 1-((3,5-Di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl) naphthalen-
145.2 (s), 137.3 (s), 135.4 (s), 134.5 (s), 133.5 (s), 130.3 (s), 129.4 (s), 2-ol (6 d). According to the general procedure, work-up and flash
128.1 (s), 126.0 (s), 125.9 (s), 117.6 (s), 114.3 (s), 68.9 (s), 56.0 (s), column chromatography (Rf = 0.4, Hexane/EtOAc: 10 : 1), product 6 d
34.4 (s), 30.4 (s). HRMS (ESI) m/z: calcd. For C30H37O2 [M + H] + : (4 h, 66.7 mg, 0.152 mmol, 76%) was obtained as a yellow solid.[14b]
1
429.2789, found: 429.2781. H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 8.01–8.03 (m, 1 H), 7.71–
7.79 (m, 2 H), 7.40–7.44 (m, 1 H), 7.23–7.33 (m, 6 H), 7.06–7.08 (m,
2,6-Di-tert-butyl-4-(phenyl(4-(prop-2-yn-1-yloxy)phenyl) meth- 1 H), 7.01 (s, 2 H), 6.29 (s, 1 H), 5.39 (s, 1 H), 5.20 (s, 1 H), 1.32 (s,
yl)phenol (4 aa). According to the general procedure, work-up and 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 153.1 (s), 153.0 (s),
flash column chromatography (Rf = 0.4, Hexane/EtOAc: 20 : 1), 142.1 (s), 136.8 (s), 133.5 (s), 131.8 (s), 129.6 (s), 129.5 (s), 129.0 (s),
product 4 aa (63.1 mg, 0.148 mmol, 74%) was obtained as a yellow 128.9 (s), 128.7 (s), 126.9 (s), 126.7 (s), 125.7 (s), 123.0 (s), 122.9 (s),
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.24–7.28 (m, 2 H), 120.3 (s), 120.0 (s), 48.6 (s), 34.4 (s), 30.2 (s).
7.15–7.19 (m, 1 H), 7.09–7.11 (m, 2 H), 7.03–7.05 (m, 2 H), 6.87–6.89
(m, 4 H), 5.39 (s, 1 H), 5.06 (s, 1 H), 4.65 (d, J = 1.2 Hz, 2 H), 2.49 (s, 4-((1H-indol-3-yl)(phenyl)methyl)-2,6-di-tert-butylphenol (6 e). Ac-
1 H), 1.35 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = cording to the general procedure, work-up and flash column
155.9 (s), 152.1 (s), 145.0 (s), 138.1 (s), 135.5 (s), 134.4 (s), 130.4 (s), chromatography (Rf = 0.5, Hexane/EtOAc: 10 : 1), product 6 e
129.4 (s), 128.2 (s), 126.0 (s), 126.0 (s), 114.6 (s), 78.8 (s), 75.4 (s), (74.9 mg, 0.182 mmol, 91%) was obtained as a white solid.[14a]
1
H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.86 (s, 1 H), 7.29–7.31 (m,
1 H), 7.11–7.25 (m, 7 H), 7.04 (s, 2 H), 6.94–6.98 (m, 1 H), 6.57–6.58

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Research Article
(m, 1 H), 5.56 (s, 1 H), 5.04 (s, 1 H), 1.36 (s, 18 H). 13C NMR (100 MHz, 2,6-Di-tert-butyl-4-((4-(diethylamino)-2-methylphenyl)
CDCl3, 25 °C, TMS): δ = 152.1 (s), 144.7 (s), 136.7 (s), 135.4 (s), (phenyl)methyl)phenol (6 k). According to the general procedure,
134.5 (s), 129.0 (s), 128.2 (s), 127.2 (s), 126.0 (s), 125.6 (s), 123.9 (s), work-up and flash column chromatography (Rf = 0.5, Hexane/EtOAc:
122.0 (s), 120.8 (s), 120.1 (s), 119.3 (s), 111.0 (s), 48.9 (s), 34.4 (s), 10 : 1), product 6 k (10 h,76.0 mg, 0.166 mmol, 83%) was obtained as
30.4 (s). a colorless oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.21–7.25
(m, 2 H), 7.13–7.16 (m, 1 H), 7.07–7.09 (m, 2 H), 6.86 (s, 2 H), 6.62–
2,6-Di-tert-butyl-4-((5-methoxy-1H-indol-3-yl)(phenyl) meth- 6.64 (m, 1 H), 6.43–6.49 (m, 2 H), 5.44 (s, 1 H), 5.02 (s, 1 H), 3.28–3.33
yl)phenol (6 f). According to the general procedure, work-up and (m, 4 H), 2.16 (s, 3 H), 1.35 (s, 18 H), 1.13 (t, J = 7.0 Hz, 6 H). 13C NMR
flash column chromatography (Rf = 0.4, Hexane/EtOAc: 10 : 1), (100 MHz, CDCl3, 25 °C, TMS): δ = 151.8 (s), 146.2 (s), 145.2 (s),
product 6 f (79.5 mg, 0.180 mmol, 90%) was obtained as a white 137.2 (s), 135.2 (s), 134.6 (s), 130.6 (s), 130.1 (s), 129.4 (s), 128.0 (s),
solid.[14a] 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.80 (s, 1 H), 126.3 (s), 125.6 (s), 114.1 (s), 109.4 (s), 52.8 (s), 44.3 (s), 34.3 (s),
7.25–7.26 (m, 4 H), 7.16–7.20 (m, 2 H), 7.05 (s, 2 H), 6.77–6.80 (m, 30.4 (s), 20.7 (s), 12.7 (s). HRMS (ESI) m/z: calcd. For C32H44NO [M +
1 H), 6.57–6.58 (m, 2 H), 5.50 (s, 1 H), 5.05 (s, 1 H), 3.64 (s, 3 H), 1.35 H] + : 458.3418, found: 458.3411.
(s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 153.6 (s),
152.0 (s), 144.6 (s), 135.4 (s), 134.5 (s), 131.9 (s), 129.0 (s), 128.2 (s), 2,6-Di-tert-butyl-4-(phenyl(phenylamino)methyl)phenol (6 l). Ac-
127.6 (s), 126.0 (s), 125.6 (s), 124.6 (s), 120.6 (s), 112.0 (s), 111.6 (s), cording to the general procedure, work-up and flash column
102.1 (s), 55.7 (s), 49.0 (s), 34.4 (s), 30.4 (s). chromatography (Rf = 0.4, Hexane/EtOAc: 10 : 1), product 6 l (8 h,
67.4 mg, 0.174 mmol, 87%) was obtained as a colorless oil. 1H NMR
2,6-Di-tert-butyl-4-((4-methoxy-1H-indol-3-yl)(phenyl) meth- (400 MHz, CDCl3, 25 °C, TMS): δ = 7.39–7.41 (m, 2 H), 7.30–7.34 (m,
yl)phenol (6 g). According to the general procedure, work-up and 2 H), 7.19–7.25 (m, 1 H), 7.07–7.12 (m, 4 H), 6.65–6.68 (m, 1 H), 6.53–
flash column chromatography (Rf = 0.5, Hexane/EtOAc: 10 : 1), 6.55 (m, 2 H), 5.40 (s, 1 H), 5.16 (s, 1 H), 4.24 (s, 1 H), 1.38 (s, 18 H).
product 6 g (81.3 mg, 0.184 mmol, 92%) was obtained as a white 13
C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 153.0 (s), 147.7 (s),
solid.[14a] 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.87 (s, 1 H), 143.1 (s), 136.0 (s), 134.1 (s), 129.1 (s), 128.6 (s), 127.1 (s), 126.9 (s),
7.18–7.24 (m, 4 H), 7.10–7.14 (m, 1 H), 7.01–7.06 (m, 3 H), 6.92–6.94 124.6 (s), 117.3 (s), 113.4 (s), 63.2 (s), 34.4 (s), 30.3 (s). HRMS (ESI)
(m, 1 H), 6.38–6.44 (m, 2 H), 5.97 (s, 1 H), 5.00 (s, 1 H), 3.58 (s, 3 H), m/z: calcd. For C27H34NO [M + H] + : 388.2635, found: 388.2631.
1.36 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 155.0 (s),
151.7 (s), 146.0 (s), 138.2 (s), 135.6 (s), 135.1 (s), 129.0 (s), 127.7 (s), 2,6-Di-tert-butyl-4-((1-methoxynaphthalen-2-yl)(phenyl) meth-
125.7 (s), 125.3 (s), 122.8 (s), 122.5 (s), 121.7 (s), 117.6 (s), 104.2 (s), yl)phenol (6 m). According to the general procedure, work-up and
100.1 (s), 55.1 (s), 49.3 (s), 34.3 (s), 30.4 (s). flash column chromatography (Rf = 0.5, Hexane/EtOAc: 10 : 1),
product 6 m (68.8 mg, 0.152 mmol, 76%) was obtained as a yellow
2,6-Di-tert-butyl-4-((5-nitro-1H-indol-3-yl)(phenyl)methyl) phenol oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 8.28–8.30 (m, 1 H),
(6 h). According to the general procedure, work-up and flash 7.95–7.97 (m, 1 H), 7.39–7.44 (m, 2 H), 7.22–7.25 (m, 2 H), 7.10–7.18
column chromatography (Rf = 0.5, Hexane/EtOAc: 10 : 1), product 6 h (m, 3 H), 6.89–6.93 (m, 2 H), 6.82–6.84 (m, 1 H), 6.70–6.72 (m, 1 H),
(78.5 mg, 0.172 mmol, 86%) was obtained as a white solid.[14a] 6.07 (s, 1 H), 5.07 (s, 1 H), 3.97 (s, 3 H), 1.34 (s, 18 H). 13C NMR
1
H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 8.51 (s, 1 H), 8.16–7.17 (m, (100 MHz, CDCl3, 25 °C, TMS): δ = 154.2 (s), 152.0 (s), 144.8 (s),
1 H), 8.03–8.05 (m, 1 H), 7.20–7.35 (m, 6 H), 7.03 (s, 2 H), 6.79–6.80 135.4 (s), 134.3 (s), 132.8 (s), 132.8 (s), 129.4 (s), 128.2 (s), 127.4 (s),
(m, 1 H), 5.59 (s, 1 H), 5.11 (s, 1 H), 1.36 (s, 18 H). 13C NMR (100 MHz,
126.4 (s), 126.0 (s), 126.0 (s), 125.9 (s), 124.7 (s), 124.3 (s), 122.4 (s),
CDCl3, 25 °C, TMS): δ = 13C{1H} NMR (100 MHz, CDCl3, 25 °C, TMS): δ =
103.0 (s), 55.4 (s), 52.7 (s), 34.3 (s), 30.4 (s). HRMS (ESI) m/z: calcd. For
152.4 (s), 143.8 (s), 141.4 (s), 139.8 (s), 135.8 (s), 133.6 (s), 128.8 (s), C32H37O2 [M + H] + : 453.2789, found: 453.2783.
128.4 (s), 126.9 (s), 126.6 (s), 126.5 (s), 125.5 (s), 123.4 (s), 117.7 (s),
117.5 (s), 111.1 (s), 48.5 (s), 34.4 (s), 30.4 (s). 2,6-Di-tert-butyl-4-((2-methoxynaphthalen-1-yl)(phenyl) meth-
yl)phenol (6 n). According to the general procedure, work-up and
2,6-Di-tert-butyl-4-((4-(dimethylamino)phenyl)(phenyl) meth- flash column chromatography (Rf = 0.4, Hexane/EtOAc: 10 : 1),
yl)phenol (6 i). According to the general procedure, work-up and product 6 n (74.2 mg, 0.160 mmol, 80%) was obtained as a yellow
flash column chromatography (Rf = 0.4, Hexane/EtOAc: 10 : 1), oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.60–7.65 (m, 2 H),
product 6 i (10 h, 67.3 mg, 0.162 mmol, 81%) was obtained as a 7.42 (s, 1 H), 7.25–7.29 (m, 3 H), 7.14–7.21 (m, 3 H), 7.08–7.10 (m,
colorless oil.[14c] 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.23–7.26
2 H), 6.96 (s, 2 H), 5.56 (s, 1 H), 5.09 (s, 1 H), 3.90 (s, 3 H), 1.35 (s,
(m, 2 H), 7.11–7.17 (m, 3 H), 6.96–6.98 (m, 2 H), 6.92 (s, 2 H), 6.66–
18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 157.4 (s), 152.1 (s),
6.68 (m, 2 H), 5.34 (s, 1 H), 5.04 (s, 1 H), 2.91 (s, 6 H), 1.36 (s, 18 H). 144.8 (s), 140.2 (s), 135.5 (s), 134.2 (s), 133.1 (s), 129.5 (s), 129.4 (s),
13
C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 151.9 (s), 148.9 (s), 128.9 (s), 128.7 (s), 128.2 (s), 127.5 (s), 126.6 (s), 126.1 (s), 126.0 (s),
145.7 (s), 135.3 (s), 134.8 (s), 133.1 (s), 129.9 (s), 129.4 (s), 128.0 (s), 118.5 (s), 105.6 (s), 56.8 (s), 55.3 (s), 34.4 (s), 30.4 (s). HRMS (ESI) m/z:
126.0 (s), 125.7 (s), 112.6 (s), 56.0 (s), 40.8 (s), 34.3 (s), 30.4 (s). calcd. For C32H37O2 [M + H] + : 453.2789, found: 453.2782.
2,6-Di-tert-butyl-4-((4-(dimethylamino)-2-fluorophenyl) 2,6-Di-tert-butyl-4-((2-methyl-4-(methylthio)phenyl)(phenyl) meth-
(phenyl)methyl)phenol (6 j). According to the general procedure, yl)phenol (6 o). According to the general procedure, work-up and
work-up and flash column chromatography (Rf = 0.4, Hexane/EtOAc: flash column chromatography (Rf = 0.4, Hexane/EtOAc: 10 : 1),
10 : 1), product 6 j (10 h, 65.9 mg, 0.152 mmol, 76%) was obtained as
product 6 o (67.5 mg, 0.156 mmol, 78%) was obtained as a yellow
a colorless oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.23–7.27
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.23–7.25 (m, 2 H),
(m, 2 H), 7.15–7.18 (m, 1 H), 7.10–7.12 (m, 2 H), 6.91 (s, 2 H), 6.75– 7.15–7.19 (m, 1 H), 7.04–7.05 (m, 3 H), 6.98–7.01 (m, 1 H), 6.82 (s,
6.79 (m, 1 H), 6.36–6.41 (m, 2 H), 5.61 (s, 1 H), 5.05 (s, 1 H), 2.91 (s, 2 H), 6.73–6.76 (m, 1 H), 5.50 (s, 1 H), 5.07 (s, 1 H), 2.45 (s, 3 H), 2.19
6 H), 1.36 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 161.5 (s, 3 H), 1.34 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ =
(d, 1J(C,F) = 241.6 Hz), 152.0 (s), 150.6 (d, 1J(C,F) = 10.7 Hz), 144.5 (s), 152.1 (s), 144.0 (s), 140.6 (s), 137.3 (s), 135.5 (s), 135.4 (s), 133.6 (s),
135.4 (s), 133.6 (s), 131.0 (d, 1J(C,F) = 6.3 Hz), 129.1 (s), 128.0 (s), 129.9 (s), 129.5 (s), 128.6 (s), 128.2 (s), 126.2 (s), 126.0 (s), 123.9 (s),
125.9 (s), 125.9 (s), 119.3 (d, 1J(C,F) = 15.4 Hz), 107.8 (s), 99.5 (d, 53.1 (s), 34.4 (s), 30.4 (s), 20.0 (s), 16.0 (s). HRMS (ESI) m/z: calcd. For
1
J(C,F) = 26.9 Hz), 48.7 (s), 40.5 (s), 34.3 (s), 30.4 (s). 19F NMR C29H37OS [M + H] + : 433.2560, found: 433.2552.
(376 MHz, CDCl3, 25 °C, TMS): δ = 116.0 (s). HRMS (ESI) m/z: calcd.
For C29H37FNO [M + H] + : 434.2854, found: 434.2848. 2,6-Di-tert-butyl-4-((5-(methylthio)thiophen-2-yl)(phenyl) meth-
yl)phenol (6 p). According to the general procedure, work-up and

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Research Article
flash column chromatography (Rf = 0.4, Hexane/EtOAc: 40 : 1), 2-(4-((3,5-Di-tert-butyl-4-hydroxyphenyl)(4-methoxyphenyl) meth-
product 6 p (62.0 mg, 0.146 mmol, 73%) was obtained as a yellow yl)benzylidene)malononitrile (7 d). According to the general proce-
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.27–7.31 (m, 2 H), dure, work-up and flash column chromatography (Rf = 0.4, Hexane/
7.21–7.24 (m, 3 H), 7.01 (s, 2 H), 6.89–6.90 (m, 1 H), 6.51–6.52 (m, EtOAc: 10 : 1) gave product 7 d (71.8 mg, 0.150 mmol, 75%) as a
1 H), 5.48 (s, 1 H), 5.11 (s, 1 H), 2.43 (s, 3 H), 1.38 (s, 18 H). 13C NMR yellow oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.81–7.83 (m,
(100 MHz, CDCl3, 25 °C, TMS): δ = 152.5 (s), 152.1 (s), 144.2 (s), 2 H), 7.72 (s, 1 H), 7.27–7.29 (m, 2 H), 6.99–7.01 (m, 2 H), 6.83–6.86
135.6 (s), 135.5 (s), 133.7 (s), 131.0 (s), 128.8 (s), 128.3 (s), 126.6 (s), (m, 4 H), 5.44 (s, 1 H), 5.13 (s, 1 H), 3.79 (s, 3 H), 1.36 (s, 18 H).
13
126.4 (s), 125.4 (s), 52.7 (s), 34.4 (s), 30.3 (s), 22.4 (s). HRMS (ESI) m/z: C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 159.7 (s), 158.3 (s),
calcd. For C26H32OS2 [M + H] + : 425.1967, found: 425.1961 153.5 (s), 152.5 (s), 135.9 (s), 135.3 (s), 132.9 (s), 130.9 (s), 130.6 (s),
130.3 (s), 128.9 (s), 125.8 (s), 114.0 (s), 113.9 (s), 112.9 (s), 81.5 (s),
2,6-Di-tert-butyl-4-((5-methoxythiophen-2-yl)(phenyl) meth- 56.2 (s), 55.3 (s), 34.4 (s), 30.3 (s). HRMS (ESI) m/z: calcd. For
yl)phenol (6 q). According to the general procedure, work-up and C32H35N2O2 [M + H] + : 479.2694, found: 479.2686.
flash column chromatography (Rf = 0.4, Hexane/EtOAc: 40 : 1),
product 6 q (56.4 mg, 0.138 mmol, 69%) was obtained as a yellow 4-((4-(1H-benzo[d]imidazol-2-yl)phenyl)(4-methoxyphenyl) methyl)-
oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.20–7.30 (m, 5 H), 2,6-di-tert-butylphenol (7 e). According to the general procedure,
7.01 (s, 2 H), 6.22–6.23 (m, 1 H), 5.97–5.98 (m, 1 H), 5.37 (s, 1 H), 5.09 work-up and flash column chromatography (Rf = 0.3, Hexane/EtOAc:
(s, 1 H), 3.82 (s, 3 H), 1.38 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, 10 : 1) gave product 7 e (96.5 mg, 0.186 mmol, 93%) as a yellow oil.
1
TMS): δ = 165.4 (s), 152.4 (s), 144.4 (s), 135.5 (s), 135.0 (s), 133.8 (s), H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 8.06–8.10 (m, 2 H), 7.51 (s,
128.8 (s), 128.2 (s), 126.4 (s), 125.5 (s), 123.2 (s), 102.6 (s), 60.1 (s), 2 H), 7.15–7.19 (m, 4 H), 6.99–7.01 (m, 2 H), 6.88 (s, 2 H), 6.79–6.81
52.6 (s), 34.4 (s), 30.3 (s). HRMS (ESI) m/z: calcd. For C26H32O2S [M + (m, 2 H), 5.39 (s, 1 H), 5.09 (s, 1 H), 3.76 (s, 3 H), 1.33 (s, 18 H).
13
H] + : 409.2196, found: 409.2191. C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 158.0 (s), 152.2 (s),
152.2 (s), 152.1 (s), 147.8 (s), 136.4 (s), 135.6 (s), 133.9 (s), 130.3 (s),
4-((3,5-Di-tert-butyl-4-hydroxyphenyl)(4-methoxyphenyl) meth- 130.2 (s), 127.6 (s), 127.6 (s), 126.6 (s), 125.9 (s), 122.8 (s), 113.7 (s),
yl)benzyl diphenylphosphinate (7 a). According to the general 55.9 (s), 55.3 (s), 34.4 (s), 30.4 (s). HRMS (ESI) m/z: calcd. For
procedure, work-up and flash column chromatography (Rf = 0.3, C35H39N2O2 [M + H] + : 519.3007, found: 519.3002.
Hexane/EtOAc: 3 : 1) gave product 7 a (98.7 mg, 0.156 mmol, 78%)
as a yellow oil. 1H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.79–7.84 2,6-Di-tert-butyl-4-((4-(di(1H-indol-3-yl)methyl)phenyl)(4-methoxy
(m, 4 H), 7.49–7.52 (m, 2 H), 7.41–7.44 (m, 4 H), 7.25–7.26 (m, 2 H), phenyl)methyl)phenol (7 f). According to the general procedure,
7.08–7.10 (m, 2 H), 7.00–7.02 (m, 2 H), 6.89 (s, 2 H), 6.80–6.82 (m, work-up and flash column chromatography (Rf = 0.3, Hexane/EtOAc:
2 H), 5.37 (s, 1 H), 5.09 (s, 1 H), 5.04 (d, J = 6.4 Hz, 2 H), 3.78 (s, 3 H), 10 : 1) gave product 7 f (94.4 mg, 0.146 mmol, 73%) as a yellow oil.
1.36 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 157.9 (s), 1
H NMR (400 MHz, CDCl3, 25 °C, TMS): δ = 7.81 (s, 2 H), 7.36–7.38 (m,
152.1 (s), 145.4 (s), 136.8 (s), 135.5 (s), 134.2 (s), 134.0 (d, J(C,P) = 2 H), 7.30–7.32 (m, 2 H), 7.21–7.23 (m, 2 H), 7.12–7.16 (m, 2 H), 6.96–
7.5 Hz), 132.2 (d, J(C,P) = 2.7 Hz), 131.7 (d, J(C,P) = 10.1 Hz), 131.4 (d, 7.03 (m, 6 H), 6.87 (s, 2 H), 6.78–6.80 (m, 2 H), 6.60 (s, 2 H), 5.83 (s,
J(C,P) = 135.8 Hz), 130.3 (s), 129.5 (s), 128.5 (d, J(C,P) = 13.1 Hz), 1 H), 5.36 (s, 2 H), 5.03 (s, 1 H), 3.76 (s, 3 H), 1.34 (s, 18 H). 13C NMR
127.7 (s), 125.9 (s), 113.5 (s), 66.2 (d, J(C,P) = 5.5 Hz), 55.8 (s), 55.2 (s), (100 MHz, CDCl3, 25 °C, TMS): δ = 157.8 (s), 151.9 (s), 142.7 (s),
34.4 (s), 30.3 (s). 31P NMR (160 MHz, CDCl3, 25 °C, TMS): δ = 32.2. 141.6 (s), 137.3 (s), 136.7 (s), 135.3 (s), 134.9 (s), 130.4 (s), 129.2 (s),
HRMS (ESI) m/z: calcd. For C41H46O4P [M + H] + : 633.3129, found: 128.5 (s), 127.1 (s), 126.0 (s), 123.6 (s), 121.9 (s), 120.0 (s), 119.9 (s),
633.3124. 119.2 (s), 113.5 (s), 111.0 (s), 55.7 (s), 55.2 (s), 39.8 (s), 34.4 (s),
30.4 (s). HRMS (ESI) m/z: calcd. For C45H47N2O2 [M + H] + : 647.3633,
2,6-Di-tert-butyl-4-((4-(1-hydroxy-2-methylbuta-2,3-dien-1- found: 647.3629.
yl)phenyl)(4-methoxyphenyl)methyl)phenol (7 b). According to the
general procedure, work-up and flash column chromatography 2,6-Di-tert-butyl-4-(hydroxy(phenyl)methyl)phenol (3 a’). According
(Rf = 0.3, Hexane/EtOAc: 10 : 1) gave product 7 b (88.2 mg, to the general procedure, work-up and flash column chromatog-
0.182 mmol, 91%) as a yellow oil. 1H NMR (400 MHz, CDCl3, 25 °C, raphy (Rf = 0.5, Hexane/EtOAc: 20 : 1) gave product 3 a’ (44.4 mg,
TMS): δ = 7.26–7.28 (m, 2 H), 7.08–7.10 (m, 2 H), 7.00–7.02 (m, 2 H), 0.142 mmol, 71%) as a yellow oil. 1H NMR (400 MHz, CDCl3, 25 °C,
6.88 (s, 2 H), 6.79–6.82 (m, 2 H), 5.38 (s, 1 H), 5.06 (s, 2 H), 4.88 (s, TMS): δ = 7.76–7.78 (m, 2 H), 7.73 (s, 2 H), 7.54–7.57 (m, 1 H), 7.45–
2 H), 3.77 (s, 3 H), 2.21 (s, 1 H), 1.56 (t, J = 3.0 Hz, 3 H), 1.35 (s, 18 H). 7.49 (m, 2 H), 5.73 (s, 1 H), 1.45 (s, 18 H). HRMS (ESI) m/z: calcd. For
13
C NMR (100 MHz, CDCl3, 25 °C, TMS): δ = 204.7 (s), 157.9 (s), C21H29O2 [M + H] + : 313.2163, found: 313.2158.
152.1 (s), 144.8 (s), 139.4 (s), 137.0 (s), 135.5 (s), 134.5 (s), 130.3 (s),
129.3 (s), 126.4 (s), 126.0 (s), 113.54 (s), 102.8 (s), 77.8 (s), 74.5 (s), 4-((3,5-Di-tert-butyl-4-hydroxyphenyl)(phenyl)methyl)phen-2,3,5,6-
55.8 (s), 55.2 (s), 34.4 (s), 30.4 (s), 14.7 (s). HRMS (ESI) m/z: calcd. For d4-ol (6 a’). According to the general procedure, work-up and flash
C33H41O3 [M + H] + : 485.3051, found: 485.3045. column chromatography (Rf = 0.5, Hexane/EtOAc: 10 : 1) gave prod-
uct 6 a’ (67.8 mg, 0.172 mmol, 86%) as a yellow oil. 1H NMR
2,6-Di-tert-butyl-4-((4-(1-hydroxy-3-phenylprop-2-yn-1-yl) (400 MHz, CDCl3, 25 °C, TMS): δ = 7.24–7.28 (m, 2 H), 7.16–7.19 (m,
phenyl)(4-methoxyphenyl)methyl)phenol (7 c). According to the 1 H), 7.09–7.11 (m, 2 H), 6.89 (s, 2 H), 5.38 (s, 1 H), 5.07 (s, 1 H), 4.77
general procedure, work-up and flash column chromatography (s, 0.7 H), 1.35 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C, TMS): δ =
(Rf = 0.4, Hexane/EtOAc: 10 : 1) gave product 7 c (87.4 mg, 153.6 (s), 153.6 (s), 152.0 (s), 145.1 (s), 137.1 (s), 135.4 (s), 134.4 h (s),
0.164 mmol, 82%) as a yellow oil. 1H NMR (400 MHz, CDCl3, 25 °C, 129.3 (s), 128.1 (s), 126.0 (s), 114.9 (s), 114.8 (s), 55.9 (s), 34.4 (s),
TMS): δ = 7.54–7.56 (m, 2 H), 7.48–7.51 (m, 2 H), 7.34–7.35 (m, 2 H), 30.3 (s).
7.29 (s, 1 H), 7.18–7.20 (m, 2 H), 7.05–7.07 (m, 2 H), 6.95 (s, 2 H),
6.84–6.86 (m, 2 H), 5.70 (s, 1 H), 5.44 (s, 1 H), 5.12 (s, 1 H), 3.81 (s,
3 H), 2.34 (s, 1 H), 1.40 (s, 18 H). 13C NMR (100 MHz, CDCl3, 25 °C,
TMS): δ = 157.9 (s), 152.1 (s), 145.7 (s), 138.2 (s), 136.8 (s), 135.5 (s), Acknowledgements
134.2 (s), 131.8 (s), 130.3 (s), 129.6 (s), 128.6 (s), 128.3 (s), 126.7 (s),
125.9 (s), 122.5 (s), 113.5 (s), 88.8 (s), 86.6 (s), 65.0 (s), 55.8 (s), This work was supported by the National Natural Science
55.3 (s), 34.4 (s), 30.4 (s). HRMS (ESI) m/z: calcd. For C37H41O3 [M + Foundation of China (21606080, 21908050), Natural Science
H] + : 533.3051, found: 533.3044. Foundation of Hunan Province (2019JJ50203), Scientific Research
Fund of the Hunan Provincial Education Department (19 A197),

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