Synthesis of bicyclic compounds was achieved via a lipase-catalysed, stereoselective, domino Michael-aldol reaction of 2-methyl-1,3-cycloalkanedione and methyl vinyl ketone. Appropriate reaction conditions, including the type of enzyme, solvent, and temperature, were determined. In addition, the effects of solvent polarity and addtives were investigated. The reaction proceeded in the presence of lipase AS in a solution of 20% acetone in dimethylsulfoxide (DMSO) at 10°C for 8 days, followed by the addition of p-toluenesulfonic acid (TsOH) to afford bicyclic compounds in 51%-83% yields with moderate stereoselectivity. Although this domino Michael-aldol reaction showed only moderate stereoselectivity, even with the acid-supported enhancement of the reaction, these results represent potential new applications for lipase.
Stereoselective Michael Reaction. -This provides the best result hitherto obtained in enantioselective syntheses of the anticoagulant warfarin using a bio-catalyst. -(SANO, K.; SAITO, S.-I.; HIROSE, Y.; KOHARI, Y.; NAKANO, H.; SEKI, C.; TOKIWA, M.; TAKESHITA, M.; UWAI*, K.; Heterocycles 87 (2013) 6, 1269-1278, http://dx.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.