TL 1998

TETRAHEDRON
LETTERS
Tetrahedron Letters 39 (1998) 7491-7494
Pergamon
Isomerizations on Silica Gel: Synthesis of Allenyl

Ketones and the First Nazarov Cyclizations of Vinyl
Allenyl Ketones
A. Stephen K. Hashmi*, Jan W. Bats, Ji-Hyun Choi, and Lothar Schwarz
lnstitut fiir Organische Chemie, Johann Wolfgang Goethe-Universitiit, Marie-Curie-Str. 11, D-60439 Frankfurt, German),
Received 24 June 1998; accepted 23 July 1998
Abstract
Dess-Martin oxidation followed by the chromatographic workup of crude, terminal propargyl ketones 5 on silica
gel directly leads to terminal allenyl ketones 6. When the other substituent on 5 was electron-rich, 7 was observed
as side-product. If the other substituent on 5 was electron-poor, the isomeric 1-propynyl ketone 8 was the side-
product. Chromatography of the crude propargyl vinyl ketones 10 on silica gel delivers the products of a Nazarov
cyclization. © 1998 Elsevier ScienceLtd. All rights reserved.
Keywords: Alkynes;Allenes; Dess-Martinreagents; Nazarovreactions
A frequently applied method for the synthesis o f allenyl ketones 1 is the oxidation o f the easily
available h o m o p r o p a r g y l i c alcohols 3 to propargyl ketones 2 f o l l o w e d by a base-catalyzed
isomerization o f 2 to 1 [~].
R2 a3 R2 R2
R3
R1 " R1 ~ R1
isomerization 7o- oxidation. OH
1 2 3
These oxidations were performed either with the Dess-Martin periodinane ( D M P ) tt'2l, Cr vL
reagents t3'41or by the Swern procedure [~]. F o r the isomerization usually aqueous sodium h y d r o g e n
carbonate tSl or triethylamine It1 was used t61. During c h r o m a t o g r a p h y on aluminium oxide as
stationary phase comparable isomerizations have been observed t7'8]. As far as propargyl ketones are
concerned, there exist only sporadic reports on such isomerizations initiated by silica gel: one o f a
0040-4039/98/$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(98)01619-0
7492
non-terminal [9] and one of terminal propargyl ketones [81. But these isomerizations seemed not to be
general, otherwise the base-induced isomerizations mentioned above would not be necessary.
In the case of terminal propargyl ketones 4, we have now observed the direct and clean
formation of 6 during the chromatographic workup of 5 on silica gel. As a control experiment we
conducted a Dess-Martin-oxidation of 4g in CDCI 3. The NMR spectra of the crude reaction
mixture showed only the signals of 5g, no 6g was detectable tl°l (the same is true for 9c, see below).
The mixture remained unchanged for one week. This probably originates from the acetic acid set
free during the Dess-Martin oxidation, in a weakly acidic medium 5 did not isomerize to 6 t4'51(in
the presence of strong acids it does) [~1].
4 5
I silica gel chromatography

o=(0
O_~ R = donor ,--- R = acceptor
R ,, R
HOAc from silica gel
DMP
8
Table 1
D e s s - M a r t i n oxidation o f 4 and subsequent c h r o m a t o g r a p h i c
w o r k u p on silica gel
4 R 7(%) 6(%) 8(%)

a 3,4-[OCH20]C6H 3 21 60 -- 03
b 3,4-(MeO)2C6H3 15 73 -- 3i ' Cll;
e 2,4,6-(MeO)3C~H 2 12 54 -- C1 CS (;B
d 3-[CH(OH)CH2C---CH]C~H4 8 45 a --
~/ ~ C CIO Ob
e 4-[CH(OH)CH=C=CH2]C6H4 7 40 ° --
f 4-(MeS)C6H4 10 60 5
g 3-(MeO)C6H4 5 67 12
h 4-(CHO)C6H 4 -- 77 4
i 4-(CO2Me)C6H 4 -- 59 5
j 4-(NO2)C6H4 -- 45 22
k 2-(NO2)C6H4 -- 41 23 Figure 1. O R T E P - p l o t o f 7 a
I 4-(MeO)C6H4CH2 b
a yield reduced due to oxidation o f the second hydroxyl group
h p r e p a r e d by a different route
7493
When this reaction mixture was directly placed on the chromatography column (without
aqueous workup, this possibility is described in the literature)t~2], the acetic acid and 5 separate and
then 5 isomerizes to 6. This separation before isomerization is necessary, when only some silica gel
was added to the reaction mixture of the Dess-Martin oxidation mentioned above, no isomerization
was observed.
While in most Dess-Martin oxidations followed by chromatographic workup exclusively 6 was
formed, in the case of substrates with electron-rich or electron-poor aryl-substituents side products
were observed (see table 1). The oxidation of 4a-4e delivered some (E)-~-acetoxy-13-methyl-enone
7a-7e. The (E)-configuration of the trisubstituted double bond in 7 was proven by two X-ray
structure determinations (7c t21 and 7a, the latter is depicted in Figure 1)t13]. When in a control
experiment acetic acid was added to 61, a similar addition was observed. Two minor side products
formed, which did not survive the chromatographic workup. So the formation of 7 is best
explained by 5 just starting to isomerize on the column while not being completely separated from
the acetic acid. On the other hand, with electron-poor substituents 4h-4k the isomerization did not
stop at 6, the tautomeric 1-propynyl ketones 8h-Sk were formed as side-products! Unexpected was
the reaction of the two substrates 4f and 4g in which both side products 7 and 8 were formed.
Ph silica
-- Ph
Et Et gel Et gel
9a 10a 11a 12a 54%
OH O O
1. DMP i, ~ silicat/~l ~
2. silicagel gel 12b
9b 59%
OH 1DMP .
E 2. silicagel Etl II gel
9c 11¢ 12¢ 24% 13 21% 14

Then we investigated the synthesis of allenyl vinyl ketones 11 from the corresponding
propargyl vinyl carbinols 9. We were unable to isolate 11 in the case of substrates having a donor
substituent tx to the ketone as in 9a-9c. Instead 12, the product of a Nazarov cyclization[14] was
obtained. Allenyl vinyl ketones have never been applied as substrates in Nazarov cyclizations
before. Usually a strong BrCnsted acid like H 2 S O 4 o r a strong Lewis acid like Fem is necessary to
7494
induce the Nazarov cyclization of divinyl ketones, donors ~ to the ketone accelerate the reaction.
In our case obviously the combination of such donors and the enhanced reactivity of the allene
allows silica gel to catalyze the Nazarov cyclization. Interestingly in ref. [8] the isomerization to
allenyl vinyl ketones bearing ¢x-donors on aluminium oxide is described to occur without
subsequent Nazarov cyclization.
If a short column was used for the chromatography, from the reaction mixtures that were
obtained from 9b or 9c, small amounts of l i b or l l c could be isolated. When l i b or l l c were
placed on a silica gel column again, they cyclized to 12b respectively 12c/13. Thus the
intermediacy of 11 in the formation of 12 was proven. On the other hand with the strong donor in
9a it was impossible to stop the reaction at the stage of l l a .
In the case of c~-substituents bearing hydrogen atoms in p-position to the carbonyl-group as in
9c, besides 12c an isomeric divinyl ketone 13 was formed (probably via tautomerization of 14).
The 3-alkylidene-2-cyclopentenones 12 obtained that way are interesting building blocks, which
recently have been described in the literature for the very first time t151.
Aknowledgement. This work was generously supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen
lndustrie.
References and Notes

[1] J~A-Marsha~X~ W a n g ~ ~rg. Chem~1992~3387-3396~J-~-Marsha~ G~.Bart~ey~J~ ~rg. Chem.1994~9~ ~69-7~7~
J. A. Marshall, C. A. Sehon, J. Org. Chem. 1997, 62, 4313-4320.
[2] A.S.K. Hashmi, L. Schwarz, Chem. Ber./Reuceil 1997, 130, 1449-1456. A. S. K. Hashmi, T. Ruppert, T. Kn6fel, J. W. Bats, J.
Org. Chem. 1997, 62, 7295-7304.
[3] Y. Fukuda H. Shiragami, K. Utimoto, H. Nozaki, J. Org. Chem. 1991, 56, 5816-5819.
[4] H.B. Henbest, Z Chem. Soc. 1952, 4536-4538.
[5] L. Brandsma, H. D. Verkruijsse, Synthesis of Acetylenes, Allenes and Cumulenes, Elsevier, Amsterdam 1981, pp 101-102 and p
236. W. D. Huntsman, T.-K. Yin, J. Org. Chem. 1983, 48, 3813-3814.
[6] C. Bruneau, P. H. Dixneuf, In Comprehensive Organic Functional Group Transformations; A. R. Katritzky, O. Meth-Coln, C. W.
Rees, eds.; Elsevier: Oxford, 1995; Vol. 1, pp 953-995, specifically p 957.
[7] S. Tsuboi, T. Masuda, A. Takeda, J. Org. Chem. 1982, 47, 4478-4482. S. Tsuboi, T. Masuda, S. Mimura, A. Takeda, Org. Synth.
Coll. Vol VIII 1993, 251-254. G. W. Kabalka, R. M. Pagni, Tetrahedron 1997, 53, 7999-8065. D. R. Taylor, Chem. Rev. 1967, 67,
317-359. H. F. Schuster, G. M. Coppola, The Chemistry of Allenes, Wiley, New York, 1984, pp 153-163. K. Kanematsu, I.
Kinnoyama, J. Chem. Soc., Chem. Commun. 1992, 735-736.
[8] R.C. Larock, M.-S. Chow, S. J. Smith, J. Org. Chem. 1986, 51, 2623-2625.
[9] T. Nagasawa, K. Taya, M. Kitamura, K. Suzuki, J. Am. Chem. Soc. 1996, 118, 8949-8950.
[10] Easily detectable by ~HNMR spectroscopy, looking at the protons of the propargyl (triplet at ~5= 2.39 and doublet at 3.85 ppm) and
the allenyl (doublet at 3 = 5.16 and triplet at 6.34 ppm) group.
[11] M. Huch6, Tetrahedron 1980, 36, 331-342.
[12] R.J. Boeckman, Jr. In Encyclopedia of Reagents for Organic Synthesis; L. A. Paquette, ed.; Wiley: Chichester, 1995; Vol 7, pp
4982-4987.
[13] Crystallographic data (excluding structure factors) for 7a has been deposited with the Cambridge Crystallographic Data Centre.
[ 14] K.L. Habermas, S. E. Denmark, Org. React. 1994, 45, 1-158. S. E. Denmark, In Comprehensive Organic Synthesis; B. M. Trost,
I. Fleming, eds.; Pergamon: Oxford, 1991; Vol. 5, pp. 751-784.
[15] Prepared by Pauson-Khand reactions. But at least one additional substituent is necessary. M. Ahmar, F. Antrax, B. Cazes,
Tetrahedron Lett. 1995, 36, 4417-4420. M. Ahmar, O. Chabanis, J. Gauthier, B. Cazes, Tetrahedron Lett. 1997, 38, 5277-5280.
M. Ahmar, C. Locatelli, D. Colombier, B. Cazes, Tetrahedron Lett. 1997, 38, 5281-5284.

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TETRAHEDRON

Isomerizations on Silica Gel: Synthesis of Allenyl

Received 24 June 1998; accepted 23 July 1998

Keywords: Alkynes;Allenes; Dess-Martinreagents; Nazarovreactions

I silica gel chromatography

4 R 7(%) 6(%) 8(%)

E 2. silicagel Etl II gel

9c 11¢ 12¢ 24% 13 21% 14

References and Notes

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