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Synthesis 2001(11): 1731-1736
DOI: 10.1055/s-2001-16746
SPECIALTOPIC
© Georg Thieme Verlag Stuttgart · New York

Bicyclic β-Lactones via Intramolecular NCAL Reactions with Cinchona Alkaloids: Effect of the C9-Substituent on Enantioselectivity and Catalyst Conformation

Guillermo S. Cortez, Seong Ho Oh, Daniel Romo*
Dept. of Chemistry, Texas A&M University, P. O. Box 30012, College Station, TX 77843-3255, USA
Fax: +1(979)8627963; e-Mail: romo@mail.chem.tamu.edu;
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Publication History

Received 2 June 2001
Publication Date:
28 September 2004 (online)

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Abstract

C9-Acylated cinchona alkaloids promote an intramolecular, nucleophile-catalyzed aldol-lactonization (NCAL) reaction leading to optically active bicyclic β-lactones. A mechanistic scheme is proposed for this catalytic, asymmetric process. Only small variations in enantioselectivity were observed for a variety of esters, a carbamate, and a carbonate at the C9 position of quinidine. A combination of coupling constants (3 J H8,H9) and nOe data was used to assign predominant solution conformations for these derivatives. Interestingly, a more rigid quinidine derivative gave a complete reversal in the sense of enantioselection.

Key words

asymmetric nucleophilic catalysis - aldol-lactonizations - 2-oxetanones - nuclear Overhauser effect - coupling constants

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Tennyson, R. L.; Cortez, G. S.; Romo, D. J. Am. Chem. Soc. 2001, accepted.