C. Bidjou et al. / Tetrahedron Letters 43 (2002) 3025–3027
3027
References
Enzymatic hydrolysis by the same lipases in phosphate
buffer10 showed the same trends. PFL PPL, SP 435
were inefficient as catalysts for hydrolysis of both ( )-
cis-2 and ( )-trans-2. Once again RGL was the most
performing (Scheme 3). At 16% conversion, hydrolysis
of ( )-trans-2 produced 10% of (+)-trans-1 (correspond-
ing to an enantioselectivity factor over 200). RGL
performed well on kinetic resolution of ( )-cis-2, pro-
ducing (+)-cis-1 of 90% e.e. at 27% conversion and 99%
e.e. at 44% conversion. This corresponds to a satisfac-
tory E>100. Interestingly, a 60:40 mixture of racemic
cis-2 and trans-2 afforded through RGL-catalyzed
hydrolysis 26% of (+)-cis-1 (94% e.e.). Only traces of
trans-1 were formed, facilitating the isolation of the
cis-alcohol.
1. Fiaud, J.-C.; Aribi-Zouioueche, L. J. Chem. Soc., Chem.
Commun. 1986, 390–392.
2. Doi, T.; Komatsu, H.; Yamamoto, K. Tetrahedron Lett.
1996, 37, 6877–6880.
3. Chautemps, P.; Pierre, J. L. Tetrahedron 1976, 32, 549–
557.
4. (a) Vedejs, E.; Dent, W. H.; Kendall, J.; Oliver, P. A. J.
Am. Chem. Soc. 1996, 118, 3556–3567; (b) Vedejs, E.;
Dent, W. H. J. Am. Chem. Soc. 1989, 111, 6861–6862.
5. Hoffmann, R. W.; Gerlach, R.; Goldmann, S. Chem. Ber.
1980, 113, 856–863.
6. To a solution of alcohol-1 (2 mmol) and isopropenyl
acetate (6 mmol) in diethyl ether (12 mL) was added the
enzyme (100 mg RGL, or 300 mg CCL, or 300 mg
SP435) and the reaction mixture was stirred at room
(18–22°C) temperature for the required time. After filtra-
tion (Celite), yields and e.e.s were measured by chiral
GLC (Chiraldex b-PM, 50 m.). The relative retention
times were, at 120°C (in min): (−)-cis-1: 73.5; (+)-cis-1:
77.5; (−)-cis-2: 69.0; (+)-cis-2: 66.0; trans-1: 47.3 and
48.8; trans-2: 52.5. The compounds were isolated through
silicagel column chromatography (heptane/ethyle acetate:
80/20).
It is worth noting that hydrolysis of ( )-cis-2 with CCL
as catalyst afforded 12% (c=0.13) of enantiomerically
pure (>99% e.e., GLC) (+)-cis-1 (corresponding to E>
200).11
In summary, both the RGL-catalyzed acylation and
hydrolysis of 2-methylene 5-t-butylcyclohexanols 1 and
their acetates 2, respectively, were diastereoselective.
The cis-compounds were more reactive than the trans
stereoisomers. This allowed us to carry out the reac-
tions onto the more readily available cis–trans mixtures
of racemic 1 or 2 and to isolate either cis or trans
material (alcohol or acetate) in high (>95%) enan-
tiomeric purities.
7. Cross, B.; Whitham, G. H. J. Chem. Soc. 1961, 1650–
1654.
8. (a) Porcine Pancreas lipase, type II, purchased from
Sigma; (b) Prepared according to: Moreau, H.; Gargouri,
Y.; Lecat, D.; Junien, J.-L.; Verger, R. Biochim. Biophys.
Acta 1988, 960, 286–293; (c) Purchased from Sigma; (d)
Novozym SP 435 (immobilized C. antarctica-B lipase)
purchased from Novo Nordisk.
9. (+)-cis-(1S,5S)-2: [h]2D0=+15.4 (c=1, ethanol).
10. To 12 mL of a phosphate buffer (pH 7) was added the
racemic acetate (2 mmol) dissolved in 2 mL diethyl ether,
followed by the enzyme. After being stirred at room
temperature for the required time, the mixture was
extracted with diethyl ether. The extracts were treated
and analyzed as above.
Acknowledgements
This work was financially supported by CMEP (AP-95
MDU 327). The Algerian Ministry of Education and
Scientific Research is gratefully acknowledged. We
thank the Sipsy company for a generous gift of rabbit
gastric lipase.
11. (+)-cis-(1R,5R)-1: [h]2D0=+8.0 (c=1, ethanol).