Highly Enantioselective Reductive Cyclization of Acetylenic Aldehydes via Rhodium Catalyzed Asymmetric Hydrogenation

Catalytic hydrogenation of acetylenic aldehydes 1a−12a using chirally modified cationic rhodium catalysts enables highly enantioselective reductive cyclization to afford cyclic allylic alcohols 1b−12b. Using an achiral hydrogenation catalyst, the chiral racemic acetylenic aldehydes 13a−15a engage in highly syn-diastereoselective reductive cyclizations to afford cyclic allylic alcohols 13b−15b. Ozonolysis of cyclization products 7b and 9b allows access to optically enriched α-hydroxy ketones 7c and 9c. Reductive cyclization of enyne 7a under a deuterium atmosphere provides the monodeuterated product deuterio-7b, consistent with a catalytic mechanism involving alkyne−carbonyl oxidative coupling followed by hydrogenolytic cleavage of the resulting oxametallacycle. These hydrogen-mediated transformations represent the first examples of the enantioselective reductive cyclization of acetylenic aldehydes.