816
N. W. Boaz / Tetrahedron: Asymmetry 10 (1999) 813–816
(RS)-cyclohexanecarboxaldehyde (NaBH4). A single stereoisomer of 3-methyl-1-cyclohexanemethanol
was prepared from monoester 3b by reduction of the acid group to afford 3-ethoxycarbonyl-1-
cyclohexanemethanol (BH3·SMe2), alcohol tosylation, and exhaustive reduction of both the tosylate
and ester groups (LiAlH4). Comparison of the materials prepared above by chiral GC indicated that
the enantiomer prepared via Lipase PS-30 hydrolysis possessed the (R) configuration at carbon three of
3-methyl-1-cyclohexanemethanol (which corresponds to carbon one of compound 3b). Thus, Lipase PS-
30 hydrolysis of diethyl cis-1,3-CHDA afforded (1R,3S)-3-ethoxycarbonylcyclohexanecarboxylic acid
[(1R,3S)-3b] and that derived from Lipase AY-30-catalyzed hydrolysis was the (1S,3R)-isomer. These
configurational assignments should likely hold true for all of the other monoesters investigated.
With this last piece of data we now can prepare either 1,3-CHDA monoethyl ester enantiomer in high
enantiomeric purity (>94% ee) and in high overall yield (>80%) with known configuration by a three-step
process involving two chemical steps and one enzymatic step.
References
1. (a) Jones, J. B.; Sabbioni, G. J. Org. Chem. 1987, 52, 4565. (b) Gais, H. J.; Lukas, K. L.; Ball, W. A.; Braun, S.; Lindner,
H. J. Liebigs Ann. Chem. 1986, 687. (c) Lam, L. K. P.; Brown, C. M.; De Jeso, B.; Lym, L.; Toone, E. J.; Jones, J. B. J.
Am. Chem. Soc. 1988, 110, 4409. (d) Schneider, M.; Engel, N.; Honicke, P.; Heinemann, G.; Gorisch, H. Angew. Chem.,
Int. Ed. Engl. 1984, 23, 67.
2. (a) Turbanti, L.; Cerbai, G.; Di Bugno, C.; Giorgi, R.; Garzelli, G.; Criscuoli, M.; Renzetti, A. R.; Subissi, A.; Bramanti,
G.; DePriest, S. A. J. Med. Chem. 1993, 36, 699. (b) Turbanti, L; Cerbai, G.; Criscuoli, M. Eur. Pat. Appl. EP 337,348,
1989. (c) Hamilton, G. S.; Huang, Z.; Yang, X. J.; Patch, R. J.; Narayaran, B. A.; Ferkany, J. W. J. Org. Chem. 1993, 58,
7263. (d) Hamilton, G. S. PCT Intl. Appl. WO 92 10,099, 1992. (e) Brion, F.; Marie, C.; Mackiewicz, P.; Roul, J. M.;
Buendia, J. Tetrahedron Lett. 1992, 34, 4889.
3. Borzilleri, R. M.; Weinreb, S. M.; Parvez, M. J. Am. Chem. Soc. 1994, 116, 9789.
4. (a) Chenevert, R.; Martin, R. Tetrahedron: Asymmetry 1992, 3, 199. (b) Chenevert, R.; Lavoie, M.; Courchesne, G.; Martin,
R. Chem. Lett. 1994, 93.
5. Allan, R. D.; Johnston, G. A. R.; Twitchin, B. Aust. J. Chem. 1981, 34, 2231.
6. Jones, D. F.; Oldham, K. Eur. Pat. Appl. EP14057, 1980.
7. Corfield, G. C.; Crawshaw, A. J. Macromol. Sci., Chem. 1971, A5, 3.