Journal of Organic Chemistry 2009-07-17

Constrained beta-proline analogues in organocatalytic aldol reactions: the influence of acid geometry.

Alan Armstrong, Yunas Bhonoah, Andrew J P White

Index: J. Org. Chem. 74(14) , 5041-8, (2009)

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Abstract

7-Azabicyclo[2.2.1]heptane-2-carboxylic acid 11 was prepared in enantiopure form, and its catalytic potential in the direct aldol reaction between acetone and 4-nitrobenzaldehyde was assessed. The bicyclic system was found to be more selective than its monocyclic analogue beta-proline 5b. A comparative density functional theory study of proline 1, beta-proline 5b, and 11 in the latter reaction revealed the origin of the improved enantioselectivity of 11 over 5b. The geometry of the carboxylic acid group in the transition states, which depended critically on pyrrolidine ring conformation, was found to play a key role.