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M. Christmann
Scheme 2. One-step synthesis of the desired pyrrolizidine carboxylic acid rac4a
obtained. Work-up with potassium carbonate in methanol afforded the
carboxylic acid 4b. We were surprised to see that the undesired cisdiastereomer 4b was formed with high selectivity. This result also suggests that the reaction does not proceed via a maleimide. When commercially available maleimide 8 was submitted to the same conditions, the
desired silylated trans-pyrrolizidine carboxylic acid rac-4a was formed.
Depending on the work-up, either tricyclic lactone 10 or carboxylic acid
4a was obtained.
We then turned our attention to the kinetic resolution of rac-4a via
an oxa-Michael lactonization. Following the seminal work of Wynberg
(Wynberg and Hiemstra 1981), many groups have contributed to the
cinchona alkaloid-catalyzed conjugate addition to Michael acceptors.
Among the nucleophiles used, soft anions usually prevail, although progress has been reported in the intramolecular oxa-Michael addition of
alcohols to α,β-unsaturated esters (Sekino et al. 2004). Interestingly, no
enantioselective addition of a carboxylic acid to a Michael acceptor has
yet been achieved. When rac-4a and quinine (2:1) are dissolved, we
M. Christmann
Scheme 2. One-step synthesis of the desired pyrrolizidine carboxylic acid rac4a
obtained. Work-up with potassium carbonate in methanol afforded the
carboxylic acid 4b. We were surprised to see that the undesired cisdiastereomer 4b was formed with high selectivity. This result also suggests that the reaction does not proceed via a maleimide. When commercially available maleimide 8 was submitted to the same conditions, the
desired silylated trans-pyrrolizidine carboxylic acid rac-4a was formed.
Depending on the work-up, either tricyclic lactone 10 or carboxylic acid
4a was obtained.
We then turned our attention to the kinetic resolution of rac-4a via
an oxa-Michael lactonization. Following the seminal work of Wynberg
(Wynberg and Hiemstra 1981), many groups have contributed to the
cinchona alkaloid-catalyzed conjugate addition to Michael acceptors.
Among the nucleophiles used, soft anions usually prevail, although progress has been reported in the intramolecular oxa-Michael addition of
alcohols to α,β-unsaturated esters (Sekino et al. 2004). Interestingly, no
enantioselective addition of a carboxylic acid to a Michael acceptor has
yet been achieved. When rac-4a and quinine (2:1) are dissolved, we