NIH Public Access

Author Manuscript
J Org Chem. Author manuscript; available in PMC 2010 March 20.
Published in final edited form as:
NIH-PA Author Manuscript

J Org Chem. 2009 March 20; 74(6): 2433–2437. doi:10.1021/jo802493k.

Synthesis of (+)-Coronafacic Acid

Douglass F. Taber*, Ritesh B. Sheth, and Weiwei Tian

Department of Chemistry & Biochemistry, University of Delaware, Newark, Delaware 19716

Abstract

An enantioselective synthesis of (+)-coronafacic acid has been achieved. Rhodium catalyzed

cyclization of an α-diazoester provided the intermediate cyclopentanone in high enantiomeric purity.
NIH-PA Author Manuscript

Subsequent Fe-mediated cyclocarbonylation of a derived alkenyl cyclopropane gave a bicyclic

enone, that then was hydrogenated and carried on to the natural product.

Introduction
Bicyclic and polycyclic ring systems are common in structurally complex and physiologically-
active natural products. Although there are many methods of preparing such ring systems, the
number of approaches to carbopolycyclic scaffolds is more limited. Corey demonstrated the
utility of an enzyme to convert 20,21-dehydro-2,3-oxidosqualene to a dehydroprotosterol.
Hajos2 employed a catalytic amount of (S)-(−)-proline in an asymmetric aldol condensation
to form optically pure bicyclic intermediates. We3 were able to demonstrate that a single
stereogenic center on the bridge between the diene and dienophile could set the absolute center
of an intramolecular Diels-Alder reaction leading to a carbobicyclic 6,6-system. Corey4
reported examples of catalytic enantioselective [2+2] cycloaddition catalyzed by chiral
aluminum bromide complexes to form 5,4-, 6,4-, and 7,4-carbobicyclic systems. We5 also
reported another approach to enantioselective polycyclic construction, utilizing Shi
epoxidation followed by selective ring opening, and then intramolecular alkylation to set the
stereogenic centers. We6 further showed in our synthesis of (+)-sulcatine G, that
NIH-PA Author Manuscript

enantiospecific C-H insertion, followed by intramolecular alkylation, could also be applied to

carbobicycle construction. Schaus7 demonstrated the utility of the Morita-Baylis Hillman
reaction, coupled with the Hosomi-Sakauri, to construct 6,6-bicyclic systems. Gaunt8 reported
a strategy using oxidative dearomatization and amine-catalyzed enantioselective
desymmetrizing Michael reaction to form 6,6-carbobicycles. In the Phillips9 synthesis of (+)-
cyanthiwigin U, tandem metathesis was used to enantioselectively construct the
polycarbocycle. Recently, Ishihara10 utilized enantioselective Robinson annulation and
cycloaddition reactions catalyzed by chiral Lewis acids for polycarbocycle construction.

We had developed (Scheme 1) a general route to enantiomerically pure 5,3- and 6,3-
carbobicyclic scaffolds by cyclization of menthyl esters such as 1 to the cyclopentanone 2.
11a Nakada11l,r,s later reported an enantioselective preparation of similar carbocyclic esters
and sulfones by copper catalyzed asymmetric intramolecular cyclopropanation. We have
improved upon our intramolecular cyclization11a by increasing the selectivity and preparative

[email protected].
 Taber et al. Page 2

yield of the cyclization. We anticipated that we could convert the ester to the alkenyl
cyclopropane 3. We speculated12 that Fe-mediated cyclocarbonylation of the alkenyl
cyclopropane could deliver the bicyclic enone 4. If this were successful, the enone 4 could then
NIH-PA Author Manuscript

be transformed in a few steps to the natural product (+)-coronafacic acid 5.

Background and Results

Coronatin 6 (Eq. 1) is a phytotoxin produced by Pseudomonas syringae. Its structure is
composed of coronafacic acid 5, a bicyclic core with three stereogenic centers, and coronamic
acid 7, a cyclopropane amino acid derived from isoleucine. Both coronatin and coronafacic
acid have been reported to mimic jasmonic acid. All three compounds induce tubers, induce
cell expansion, inhibit cell division, and promote senescence in plants.13 While there were 15
previous total syntheses of coronafacic acid,14 only one enantioselective route had been
reported.14m
NIH-PA Author Manuscript

(1)

Intramolecular Cyclopropanation
Dirhodium tetracarboxylate catalysts are known to cyclize α-diazo esters, such as 1. Earlier,
we had cyclized 1 to a 1:1 mixture of 2 and 8 (Eq. 2), using a copper bronze catalyst.11a We
separated the menthyl esters 2 and 8 by column chromatography, leading to pure 2 in 21%
yield. We have investigated a diverse selection of dirhodium tetracarboxylate catalysts to
improve upon those earlier results.
NIH-PA Author Manuscript

(2)

We have found (Table 1) that, by using Rh (II) catalysts, we could induce some
diastereoselectivity in this cyclization. We found that dirhodium pivalate at room temperature
provided the best preparative yield, 63%, of the desired cyclopentanone 2.

Preparation of alkenyl cyclopropane 6

With the initial two stereocenters set, we protected (Scheme 2) the ketone as the ketal 9.
Attempts to reduce the ester directly to the aldehyde with less than an equivalent of lithium
aluminum hydride or with DIBAL delivered a mixture of alcohol, aldehyde, and the starting
ester. We found that completely converting the ester 2 to the alcohol followed by oxidization

J Org Chem. Author manuscript; available in PMC 2010 March 20.

 Taber et al. Page 3

to aldehyde 10 with Dess-Martin reagent was more effective. We were then able to perform a
Wittig reaction on aldehyde 10 to give alkenyl cyclopropane 3.
NIH-PA Author Manuscript

Preparation of enone 9
We12b,c,d had reported the preparation of 2,5 and 5-substituted cyclohexenones via Fe-
mediated cyclocarbonylation. More recently, we found that we could couple the Wittig reaction
with Fe-mediated cyclocarbonylation to convert aldehydes to 2-substituted cyclohexenones.
12e Sarel12a demonstrated the photochemical expansion of a methylene spiroalkane 11 to the
bicyclic enones 12 and 13 in his studies of (+)-α-thujene (Eq. 3). The cyclocarbonylation to a
bicyclic enone from a 5,3- or 6,3-ring fused alkenyl cyclopropane such as 3 had not yet been
reported.

(3)

We found (Eq. 4) that UV irradiation of 3 in the presence of Fe(CO)5 converted the alkenyl
cyclopropane 3 to the bicyclic cyclohexenone 4 in low yield with accompanying deketalization.
NIH-PA Author Manuscript

We found that by adding K2CO3 to the irradiation, the reaction was buffered and ketal
deprotection was avoided. The use of tetrahydrofuran, rather than isopropanol,12b–e as the
reaction solvent doubled the conversion of 3 to 4. We found it practical to run the
cyclocarbonylation to about 40% conversion (TLC), as longer irradiation led to diminished
yield. The unreacted starting material was easily separated and recycled.

The kinetic product from the cyclocarbonylation was the β,γ-unsaturated ketone. This was not
purified, but was converted to the desired α,β-unsaturated ketone 4 by stirring for an hour at
room temperature with DBU.
NIH-PA Author Manuscript

(4)

Synthesis of (+)-Coronafacic Acid

Pd-mediated hydrogenation of the cyclohexenone 4 (Scheme 4) at ambient temperature and
pressure provided the bicyclic ketone 11 as a single diastereomer. Carbomethoxylation
followed by reduction with sodium borohydride gave the alcohol 12 as a mixture of
diastereomers. Dehydration of the mixture by mesylation and subsequent addition of DBU
gave the ketal-protected coronafacic methyl ester 13 as a single diastereomer. Deprotection
and ester hydrolysis were then completed in one step with aqueous HCl at reflux to give the

J Org Chem. Author manuscript; available in PMC 2010 March 20.

 Taber et al. Page 4

natural product 5. The physical data, including optical rotation (obs., [α]20D +104, lit.,14o
[α]20D +105) were consistent with those previously reported for (+)-coronafacic acid.
NIH-PA Author Manuscript

Conclusion
We have completed an enantioselective synthesis of (+)-coronofacic acid. We were able to set
the initial two stereogenic centers utilizing rhodium catalyzed intramolecular
cyclopropanation. We were then able to expand the cyclopropane utilizing Fe-mediated
cyclocarbonylation. We expect that this will be a general route to enantiomerically pure 6,5-
and 6,6-carbobicyclic systems.

Experimental Section
(1S,2R,5S)-5-Methyl-2-(propan-2-yl)cyclohexyl 2-oxobicyclo[3.1.0]hexane-1-carboxylate 2
and 8
Rh (Piv) 15a (5 mg) was added to α-diazoester 111a (6.12 g, 20 mmol) in 20 mL of dry
2 4
CH2Cl2 (1.0 M) at rt. The solution was stirred at rt for 1 h, and then additional Rh2(Piv)4 (5
mg) was added and the reaction was allowed to stir for an additional 2 h. The mixture was
concentrated and the residue chromatographed using 94:6 hexanes/EtOAc as elution solvent
to give the cyclopentanone 2 (3.61 g, 63% yield) and 8 (1.78 g, 32% yield) as an oil.
Cyclopentanone 2 was then crystallized at −78°C in petroleum ether (5 mL) to give 2 (3.49 g,
NIH-PA Author Manuscript

62% as a white crystalline solid, mp = 34–36°C, [α]20D +47.2 (c=1.0, CH2Cl2); TLC Rf = 0.27
(9:1 hexanes/EtOAc); 1H NMR δ4.71 (dt, J = 4.9, 11.5 Hz, 1H), 2.54 (m, 1H), 2.22 (m, 3H),
2.01 (m, 4H), 1.68 (d, J = 12.1 Hz, 2H), 1.34–1.48 (m, 3H), 0.88–1.05 (m, 9H), 0.75 (d, J= 7.6
Hz, 3H); 13C NMR δ u:16 207.0, 167.6, 40.6, 37.8, 34.2, 33.5, 21.4, 21.0; d: 74.9, 46.8, 32.4,
31.3, 25.8, 23.1, 21.9, 20.8, 16.0; IR 2952, 1736, 1454, 1383, 1311 cm−1; MS m/z (%) 279 (M
+H, 100), 263 (48), 141 (98), 123 (79); HRMS: Calcd for C17H27O3 (M+H) 279.1960, obsd
279.1967. For cyclopentanone 8: (1.45 g, 27% as an oil, [α]20D −47.0 (c=1.0, CH2Cl2); TLC
Rf = 0.25 (9:1hexanes/EtOAc); 1H NMR δ 4.65 (dt, J = 4.9, 11.5 Hz, 1H), 2.49 (m, 1H), 2.16
(m, 3H), 1.93 (m, 3H), 1.75 (m, 1H), 1.60 (d, J = 12.1 Hz, 2H), 1.34–1.48 (m, 3H), 0.88–1.05
(m, 9H), 0.67 (d, J = 7.6 Hz, 3H); 13C NMR δu: 207.0, 167.6, 40.7, 37.7, 34.2, 33.6, 21.6, 20.7;
d: 74.9, 46.8, 32.2, 31.3, 26.2, 23.4, 22.0, 20.9, 16.3; IR 2950, 1735, 1454, 1384, 1311 cm−1;
MS m/z (%) 279 (M+H, 100), 263 (49), 141 (98), 123 (79); HRMS: Calcd for C17H27O3 (M
+H) 279.1960, obsd 279.1967.

Ketal 9
2, 2-Dimethyl-1,3-propanediol (2.11g, 24 mmol), p-toluenesulfonic acid monohydrate (5 mg,
0.02 mmol), and cyclopentanone 2 (3.33 g, 12 mmol) were combined in 24 mL of dry toluene.
NIH-PA Author Manuscript

The solution was maintained at reflux for 8 h. The reaction was concentrated, and the residue
was chromatographed to give the ketal 6 (3.89 g, 89% yield) as a white solid, mp = 97–99°C;
[α]20D +32.1(c=1.0, CH2Cl2); TLC Rf = 0.49 (8:2 petroleum ether/MTBE); 1H NMR δ 4.69
(dt, J = 4.9, 11.5 Hz, 1H), 3.62 (d, J =11.2 Hz, 1H), 3.47 (m, 3H), 2.43 (dd, J =8.2, 13.6 Hz,
1H) 1.87–2.10(m, 4H), 1.66–1.74 (m, 3H), 1.39–1.48 (m, 5H), 1.14 (m, 2H), 1.06 (m, 3H),
0.868–1.05 (m, 7H), 0.74 (m, 6H); 13C NMR δ u: 170.6, 107.1, 73.2, 71.7, 40.7, 37.0, 34.5,
30.2, 25.2, 23.6, 23.3, 23.0, 16.8; d: 74.3, 47.0, 31.4, 26.0, 24.6, 22.1, 22.0, 20.8, 16.4; IR 2950,
1705, 1455, 1384, 1309 cm−1; MS m/z (%) 365 (M+H, 87), 279 (7), 227 (100), 209 (63), 182
(36), 141 (65), 128 (60); HRMS: Calcd for C22H36O4 364.2614, obsd 364.2623.

(1S,5R)-5′,5′-Dimethyl-1H-spiro[bicyclo[3.1.0]hexane-2,2′-[1,3]dioxane]-1-carbaldehyde 10
LiAlH4 (1.0 M Solution in THF, 12 mL, 12 mmol) was added over 10 min to ketal 9 (3.64 g,
10 mmol) in 10 mL (1.0 M) of dry THF at rt The solution was stirred at rt for 2 h. Ethyl acetate
(5 mL) was added dropwise over 30 minutes followed by sodium sulfate decahydrate (3.2 g,

J Org Chem. Author manuscript; available in PMC 2010 March 20.

 Taber et al. Page 5

10 mmol). The mixture was stirred at rt for 2 h, then filtered through a pad of silica gel with
ethyl acetate (20 mL) and concentrated. The residue was chromatographed to give the crude
alcohol. Dess-Martin periodinane (4.24 g, 11 mmol) was added to the alcohol in 10 mL of dry
NIH-PA Author Manuscript

dichloromethane at rt. The mixture was concentrated and the residue was chromatographed to
give the aldehyde 10 (1.62 g, 77% yield from 9) as an oil, TLC Rf = 0.34 (8:2 petroleum ether/
MTBE); [α]20D −59.1 (c=1.0, CH2Cl2); 1H NMR δ 10.36 (s, 1H), 3.72 (d, J = 11.2 Hz, 1H),
3.54 (d, J =11.2 Hz, 1H), 3.48 (s, 2H), 2.47 (dd, J =8.6, 14.3 Hz, 1H), 2.07 (m, 1H), 1.90 (m,
1H), 1.79 (m, 1H), 1.49 (dd, J =5.2, 13.0 Hz, 1H), 1 30 (m, 3H), 1.17 (m, 2H), 0.77 (s,
3H); 13C NMR δ u: 107.7, 73.3, 71.6, 44.8, 30.0, 25.6, 24.2, 18.6; d: 201.1, 30.5, 22.9, 22.0;
IR 2953, 1700, 1467, 1335, 1116 cm−1; MS m/z (%) 211 (M+H, 58), 181 (55), 141 (67), 123
(100); HRMS: Calcd for C12H18O3 210.1256, obsd 210.1262.

(1S,5R)-1-[(1Z)-But-1-en-1-yl]-5′,5′-dimethylspiro[bicyclo[3.1.0]hexane-2,2′-[1,3]dioxane] 3
Potassium t-butoxide (1.0 M solution in THF, 20 mL, 20 mmol) was added over 20 min to a
suspension of propyltriphenylphosphonium bromide (3.50 g, 9 mmol) in 20 mL of dry THF at
0°C. The external cooling was removed and the mixture was stirred for 30 min. The aldehyde
10 (1.57 g, 7.5 mmol) was added, and the mixture was stirred at rt for 1 h. The mixture was
quenched with water (50 mL) and then partitioned between water and EtOAc. The combined
organic extract was dried (MgSO4) and concentrated. The residue was chromatographed to
give the alkenyl cyclopropane 3 (1.84 g, 78% yield) as an oil, [α]20D +20.8 (c=1.0, CH2Cl2);
TLC Rf = 0.74 (8:2 petroleum ether/MTBE); 1H NMR δ 5.70 (d, J = 8.0 Hz, 1H), 5.48 (m, 1H),
NIH-PA Author Manuscript

3.56 (d, J =11.6 Hz, 1H), 3.43 (d, J =11.6 Hz, 1H), 3.40 (s, 2H), 2.18–2.29 (m, 3H), 1.93 (m,
1H), 1.72 (dd, J =8.0, 12.0 Hz, 1H), 1.41 (m, 1H), 1.17 (m, 4H), 0.95 (t, J =7.2 Hz, 3H), 0.85
(m, 1H), 0.71 (s, 3H), 0.65 (dd, J =4.2, 7.2 Hz, 1H); 13C NMR δ u: 110.0, 73.1, 71.4, 33.2,
30.1, 24.7, 24.6, 21.8, 14.7; d: 136.6, 125.5, 22.7, 22.5, 22.1, 14.3; IR 2950, 2859, 1211, 1153,
1117 cm−1; MS m/z (%) 237 (M+H, 18), 201 (100), 183 (54), 141 (71); HRMS: Calcd for
C15H24O2 236.1776, obsd. 236.1767.

(3a′R,7a′R)-6′-Ethyl-5,5-dimethyl-2′,3′,3a′,7a′-tetrahydrospiro[1,3-dioxane-2,1′-inden]-5′(4′H)-
one 4
To the alkenyl cyclopropane 3 (236 mg, 1.0 mmol) and potassium carbonate (280 mg, 2.0
mmol) in 10 mL of 2-propanol and 5 mL of tetrahydrofuran (0.075 M) was added Fe(CO)5
(392 mg, 2.0 mmol). The Pyrex reaction vessel was purged with CO, a CO balloon was attached,
and the mixture was irradiated for 4 h at room temperature as a thin film in a Rayonet apparatus
(300 nm) set for autocooling. The reaction was halted every hour to agitate the tube inside the
larger tube, after which photolysis was restarted. At the end of the irradiation, DBU (304 mg,
2.0 mmol) was added, and the mixture was stirred at room temperature for 1 h under nitrogen.
The mixture was diluted with 40 mL of EtOAc and filtered through a small pad of packed silica
NIH-PA Author Manuscript

gel. The eluate was concentrated and the residue was chromatographed to give 152 mg of
unreacted 3 and 90 mg of 4 (98% yield based on 3 not recovered) as an oil, [α ]20D +102.5
(c=1.0, CH2Cl2); TLC Rf= 0.30 (8:2 petroleum ether/MTBE); 1H NMR δ 6.45 (s, 1H), 3.45
(m, 4H), 2.95 (br s, 1H), 2.64 (m, 1H), 2.41 (m, 2H), 2.17 (m, 2H), 1.70– 1.97 (m, 3H), 1.35
(m, 1H), 0.95 (m, 6H), 0.85 (m, 3H); 13C NMR δ u: 198.4, 140.7, 108.2, 71.4, 70.7, 39.9, 30.5,
29.3, 25.0, 21.7; d: 138.9, 45.0, 33.1, 21.5, 21.3, 12.1; IR 2952, 1672, 1493, 1312, 1153
cm−1; HRMS: Calcd for C16H24O3 264.1725, obsd. 264.1731.

(3a′R,6′R,7a′S)-6′-Ethyl-5,5-dimethylhexahydrospiro[1,3-dioxane-2,1′-inden]-5′(4′H)-one 14
Pd/C (5 wt%, 10 mg) was added to the bicyclic enone 4 (85 mg, 0.32 mmol) in 5 mL of
methanol. The reaction vessel was purged with hydrogen, a hydrogen balloon was attached,
and the mixture was stirred at rt for 4 h until the TLC indicated disappearance of the UV
absorbent spot. The mixture was filtered through a plug of Celite and concentrated. The residue

J Org Chem. Author manuscript; available in PMC 2010 March 20.

 Taber et al. Page 6

was chromatographed to give 11 (81 mg, 95% yield) as an oil, [α]20D +124.6 (c=1.0,
CH2Cl2), TLC Rf = 0.30 (8:2 petroleum ether/MTBE); 1H NMR δ 3.48 (m, 4H), 2.62 (m, 1H),
2.51 (m, 2H), 2.25 (dd, J =5.6, 14.4 Hz, 1H), 2.15 (m, 1H), 2.00 (m, 3H), 1.82 (m, 2H), 1.46
NIH-PA Author Manuscript

(m, 1H), 1.24 (m, 2H), 1.04 (m, 3H), 0.91 (m, 6H); 13C NMR δ u: 214.2, 109.6, 72.4, 71.5,
43.8, 30.7, 30.0, 28.3, 26.6, 22.3; d: 49.2, 44.3, 37.1, 22.5, 11.6; HRMS: Calcd for
C16H26O3 266.1882, obsd 266.1880.

Methyl (3a′S,5′S,6′R,7a′S)-6′-ethyl-5′-hydroxy-5,5-dimethyloctahydrospiro[1,3-dioxane-2,1′-
indene]-4′-carboxylate 15
Sodium hydride (60%, 24 mg, 0.6 mmol) and dimethyl carbonate (3 mL, 35 mmol) were heated
to reflux for 20 min. A drop of methanol was added via an addition funnel over a condenser
and stirred at reflux for 5 min. Bicyclic ketone 14 (80 mg, 0.3 mmol) in 1 mL dry toluene was
added via an addition funnel over a condenser, and the mixture was stirred at reflux for 3 h.
The mixture was cooled to rt and quenched with saturated aqueous NH4Cl and then partitioned
between water and EtOAc. The combined organic extract was dried (MgSO4) and concentrated.
The residue was dissolved in methanol (5 mL) and NaBH4 (19 mg, 0.5 mmol) was added. The
mixture was stirred at rt for 2 h. The mixture was concentrated and the residue was
chromatographed to give alcohol 15 (44 mg, 45% yield) as an oil, [α]20D+10.4 (c=1.0,
CH2Cl2); TLC Rf = 0.19 (8:2 petroleum ether/MTBE); 1H NMR δ 4.17 (s, 1H), 3.72 (s, 3H),
3.50 (s, 2H), 3.42 (s, 2H), 2.64 (m 1H), 2.56 (m, 1H), 2.21 (m, 2H), 2.01 (m, 1H), 1.92 (m,
1H), 1.56 (m, 3H), 1.38 (m, 4H), 0.95 (m, 9H); 13C NMR δ u: 176.1, 109.5, 72.7, 71.0, 31.6,
NIH-PA Author Manuscript

30.1, 30.0, 25.3, 22.3; d: 67.6, 51.7, 46.8, 44.5, 42.0, 36.5, 22.5, 11.7; IR 3488, 2913, 1713,
1289, 1152 cm−1; MS m/z (%) 327 (M+H, 6), 141 (100); HRMS: Calcd for C18H30O5
326.2093, obsd 326.2095.

Methyl (3a′S,6′R,7a′S)-6′-ethyl-5,5-dimethyl-2′,3′,3a′,6′,7′,7a′-hexahydrospiro[1,3-
dioxane-2,1′-indene]-4′-carboxylate 16
Methanesulfonyl chloride (60 mg, 0.36 mmol) was added slowly to alcohol 12 (40 mg, 0.12
mmol) and triethylamine (1 mL, 7.2 mol) in 1 mL of dichloromethane at 0°C. The solution
was stirred to rt over 2 h. DBU (2 mL, 2.04g, 14 mmol) was added and the solution was stirred
at rt for 18 h. The solution was filtered through a pad of silica gel with EtOAc and concentrated.
The residue was chromatographed to give ketal ester 15 (21 mg, 56% yield) as an oil, [α]20D
+25.5 (c=1.0, CH2Cl2); TLC Rf = 0.44 (8:2 petroleum ether/MTBE); 1H NMR δ 6.84 (s, 1H),
3.72 (s, 3H), 3.52 (s, 2H), 3.45 (d, J =4.4 Hz, 2H), 2.95 (m 1H), 2.34 (m, 1H), 2.12 (m, 3H),
1.84 (m, 2H), 1.47 (m, 4H), 0.98 (m, 9H); 13C NMR δ u: 185.1, 133.3, 109.5, 72.9, 71.2, 31.2,
30.1, 28.2, 27.7, 25.9; d: 143.2, 51.8, 42.8, 38.1, 36.0, 22.5, 11.3; IR 2958, 1714, 1440, 1249
cm−1; MS m/z (%) 309 (M+H, 8), 279 (7), 237 (12), 222 (94), 209 (37), 165 (55), 141 (100),
119 (99); HRMS: Calcd for C18H29O4 (M+H) 309.2066, obsd. 309.2066.
NIH-PA Author Manuscript

(+)-Coronafacic Acid 5
Hydrochloric acid (20% aqueous, 2 mL) was added to ketal ester 16 (11 mg, 0.07 mmol). The
mixture was heated to reflux for 4 hours. The solution was allowed to cool to rt then partitioned
between water and EtOAc. The combined organic extract was dried (MgSO4) and concentrated.
The residue was chromatographed to give 5 (7 mg, 55% yield) as an oil, TLC Rf = 0.25 (7:3
petroleum ether/EtOAc).; [α]20D +104 (c=0.1, MeOH), lit.,14o [α]20D +105. The spectroscopic
data of the natural product 5 were compared with those of earlier syntheses14o and found to
be identical.

Supplementary Material
Refer to Web version on PubMed Central for supplementary material.

J Org Chem. Author manuscript; available in PMC 2010 March 20.

 Taber et al. Page 7

Acknowledgements
We thank John Dykins for high-resolution mass spectrometry under the financial support of NSF 054177. We thank
NIH-PA Author Manuscript

the NIH (GM060287) for financial support of this work.

References
1. Corey EJ, Lin K, Yamamoto H. J Am Chem Soc 1969;91:2132. [PubMed: 5784177]
2. Hajos ZG, Parrish DR. J Org Chem 1974;39:1615.
3. Taber DF, Gunn BP. J Am Chem Soc 1979;101:3992.
4. Corey EJ, Canales E. J Am Chem Soc 2007;129:12686. [PubMed: 17900126]
5. Taber DF, He T, Xu M. J Am Chem Soc 2004;126:13900. [PubMed: 15506732]
6. Taber DF, Frankowski KJ. J Org Chem 2005;70:6417. [PubMed: 16050704]
7. Pfeiffer MWB, Phillips AJ. J Am Chem Soc 2005;127:5334. [PubMed: 15826167]
8. Rodgen SA, Schaus SE. Angew Chem, Int Ed 2006;45:4929.
9. Vo NT, Pace RDM, O’Hara F, Gaunt MI. J Am Chem Soc 2008;130:404. [PubMed: 18081291]
10. Ishihara K, Fushimi M. J Am Chem Soc 2008;130:7532. [PubMed: 18494473]
11. For previous preparations of cyclohexanones and cyclopentanones via intramolecular
cyclopropanation, see (a) Taber DF, Saleh SA, Korsmeyer RW. J Org Chem 1980;45:4699. (b) Taber
DF, Malcolm SC. J Org Chem 1998;63:3717. (c) Dauben WG, Hendricks RT, Luzzio MJ, Ng HP.
Tetrahedron Lett 1990;31:6969. (d) Pique C, Fahndrich B, Pfaltz A. Synlett 1995;(Special):491. (e)
NIH-PA Author Manuscript

Park SW, Son JH, Kim SG, Ahn KH. Tetrahedron: Asymmetry 1999;10:1903. (f) Kim SG, Cho CW,
Ahn KH. Tetrahedron 1999;55:10079. (g) Barberis M, Estevan F, Lahuerta P, Perez-Prieto J, Sanau
M. Inorg Chem 2001;40:4226. [PubMed: 11487326] (h) Barberis M, Prieto J, Stiriba SE, Lahuerta
P. Org Lett 2001;3:3317. [PubMed: 11594823] (i) Saha B, Uchida T, Katsuki T. Chem Lett
2002;8:846. (j) Barberis M, Perez-Prieto J, Herbst K, Lahuerta P. Organometallics 2002;21:1667.
(k) Saha B, Uchida T, Katsuki T. Tetrahedron: Asymmetry 2003;14:823. (l) Honma M, Sawada T,
Fujisawa Y, Utsugi M, Watanabe H, Umino A, Matsumura T, Hagihara T, Takano M, Nakada M. J
Am Chem Soc 2003;125:2860. [PubMed: 12617637] (m) Honma M, Nakada M. Tetrahedron Lett
2003;44:9007. (n) Wong A, Welch CJ, Kuethe JT, Vazquez E, Shaimi M, Henderson D, Davies IW,
Hughes DL. Org Biomol Chem 2004;2:168. [PubMed: 14737638] (o) Estevan F, Lahuerta P, Lloret
J, Perez-Prieto J, Werner H. Organometallics 2004;23:1369. (p) Estevan F, Lahuerta P, Lloret J,
Penno D, Sanau M, Ubeda MA. J Organomet Chem 2005;690:4424. (q) Uchida T, Katsuki T.
Synthesis 2006:1715. (r) Ida R, Nakada M. Tetrahedron Lett 2007;48:4856. (s) Takeda H, Honma
M, Ida R, Sawada T, Nakada M. Synlett 2007;4:579.
12. For the development of Fe-mediated cyclocarbonylation, see: (a) Victor R, Ben-Shoshan R, Sarel S.
J Org Chem 1978;43:4971. (b) Taber DF, Kanai K, Jiang Q, Bui G. J Am Chem Soc 2000;122:6807.
(c) Taber DF, Bui G, Chen B. J Org Chem 2001;66:3423. [PubMed: 11348125] (d) Taber DF, Joshi
PV, Kanai K. J Org Chem 2004;69:2268. [PubMed: 15049618] (e) Taber DF, Sheth RB. J Org Chem
2008;73:8030. [PubMed: 18816101]
NIH-PA Author Manuscript

13. For a recent review of chemistry and biological properties of coronatin and coronafacic acid, see
Mitchell RE. Chem N Z 2004;68:24.
14. For previous coronafacic acid syntheses, see (a) Ichihara A, Kimura R, Moryasu K, Sakamura S.
Tetrahedron Lett 1977;18:4331. (b) Jung ME, Hudspeth JP. J Am Chem Soc 1980;102:2463. (c)
Ichihara A, Kimura R, Moryasu K, Sakamura S. J Am Chem Soc 1980;102:6353. (d) Tsuji J. Pure
Appl Chem 1981;53:2371. (e) Jung ME, Halweg KM. Tetrahedron Lett 1981;22:2735. (f) Nakayama
M, Ohira S, Okamura Y, Soga S. Chem Lett 1981:731. (g) Nakayama M, Ohira S. Agric Biol Chem
1983;47:1689. (h) Liu HJ, Brunet ML. Can J Chem 1984;62:1747. (i) Bhamare NK, Granger T,
Macas TS, Yates P. J Chem Soc, Chem Commun 1990:739. (j) Mehta G, Praveen M. J Chem Soc,
Chem Commun 1993:1573. (k) Hoelder S, Blechert S. Synlett 1996:505. (l) Nara S, Toshima H,
Ichihara A. Tetrahedron Lett 1996;37:6745. (m) Nara S, Toshima H, Ichihara A. Tetrahedron
1997;53:9509. (n) Sono M, Hashimoto A, Nakashima K, Tori M. Tetrahedron Lett 2000;41:5115.
(o) Mehta G, Reddy DS. J Chem Soc, Perkin Trans I 2001;10:1153. (p) Moreau B, Ginisty M,
Alberico D, Charette AB. J Org Chem 2007;72:1235. [PubMed: 17256906]

J Org Chem. Author manuscript; available in PMC 2010 March 20.

 Taber et al. Page 8

15. For rhodium (II) complexes, see (a) piv = pivalate, see Handa M, Takata A, Nakao T, Kasuga K,
Mikuriya M, Kotera T. Chem Lett 1992;10:2085. tfa = trifluoroacetate, see (b) Duddeck H, Ferguson
G, Kaitner B, Kennedy M, McKervey MA, Maguire AR. J Chem Soc, Perkin Trans I 1990;4:1055.
NIH-PA Author Manuscript

oct = octanoate, see (c) Giroud-Godquin AM, Marchon JC, Guillon D, Skoullos A. J Phys Chem
1986;90:5502.Ph3CO2 = triphenylacetate, see (d) Hashimoto S, Watanabe N, Ikegami S. Tetrahedron
Lett 1992;33:2709.OAc = aceto, see (e) Rempel GA, Legzdins P, Smith H, Wilkinson G. Inorg Synth
1971;13:90.Esp = bis [rhodium (α, α, α′, α′-tetramethyl-1,3-benzenedipropionate)], see (f) Espino
CG, Flori KW, Kim M, Du Bois JD. J Am Chem Soc 2004;126:15378. [PubMed: 15563154]R-ptpa
= dirhodium tetrakis [N-phthaloyl-(R)-phenylalaninate], see (g) Okada Y, Minami Y, Miyamoto M,
Otaguro T, Sawasaki S, Ichikawa J. Heteroatom Chem 1995;6:195.R-pttl = dirhodium tetrakis
[(2R)-3,3-dimethyl-2-(phthalimido)butanoateo], see (h) Tsutsui H, Yamaguchi Y, Kitagaki S,
Nakamora S, Anada M, Hashimoto S. Tetrahedron: Asymmetry 2003;14:817.S-dosp = dirhodium
tetrakis [(S)-(−)-N-p-dodecylphenylsulfonyl)prolinato], see (i) Davies HML, Bruzinkski P,
Hutcheson DK, Kong N, Fall MJ. J Am Chem Soc 1996;118:6897. (j) S-tbsp = dirhodium tetrakis
[1-[(4-tert-butylphenyl)sulfonyl]-(2S)-pyrrolidinecarboxylate], see ref. 14i.
16. 13C multiplicities were determined with the aid of a JVERT pulse sequence, differentiating the signals
for methyl and methine carbons as “d” and for methylene and quaternary carbons as “u”.
NIH-PA Author Manuscript
NIH-PA Author Manuscript

J Org Chem. Author manuscript; available in PMC 2010 March 20.

 Taber et al. Page 9
NIH-PA Author Manuscript
NIH-PA Author Manuscript

SCHEME 1.
NIH-PA Author Manuscript

J Org Chem. Author manuscript; available in PMC 2010 March 20.

 Taber et al. Page 10
NIH-PA Author Manuscript
NIH-PA Author Manuscript

SCHEME 2.
NIH-PA Author Manuscript

J Org Chem. Author manuscript; available in PMC 2010 March 20.

 Taber et al. Page 11
NIH-PA Author Manuscript
NIH-PA Author Manuscript

SCHEME 3.
NIH-PA Author Manuscript

J Org Chem. Author manuscript; available in PMC 2010 March 20.

 NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Table 1
Cyclization of Diazo Menthyl Ester 1

Entry Rhodium Ligand Solvent Temperature (°C) Diastereoselectivity (2:8) Yield (%)a

1 pivb CH2Cl2 25 2.5:1 95

Taber et al.

2 pivb PhCH3 25 1.5:1 91

3 pivb C6H12 25 1.2:1 80

4 pivb CCl4 25 1.2:1 70

5 pivb CH2Cl2 −78 3.0:1 90

6 tfac CH2Cl2 25 0.9:1 70

7 octd CH2Cl2 25 1.2:1 89

8 Ph3CCO2e CH2Cl2 25 0.7:1 75

9 OAcf CH2Cl2 25 1.0:1 80

10 Espg CH2Cl2 25 1.3:1 88

11 R-ptpah CH2Cl2 25 1.7:1 71

12 R-pttli CH2Cl2 25 1.3:1 82

13 S-dospj CH2Cl2 25 1.7:1 91

14 S-tbspk CH2Cl2 25 1.5:1 89

a
Yields reported are for the isolated mixture of the two diastereomers.
b
See ref. 15a.
c
See ref 15b.

J Org Chem. Author manuscript; available in PMC 2010 March 20.

d
See ref 15c.
e
See ref 15d.
f
See ref 15e.
g
See ref 15f.
h
See ref 15g..
i
See ref 15h.
j
See ref 15i.
Page 12
 Taber et al. Page 13
NIH-PA Author Manuscript
NIH-PA Author Manuscript
NIH-PA Author Manuscript

See ref 15j.

k

J Org Chem. Author manuscript; available in PMC 2010 March 20.