Abstract
In the pursuit of mechanism- and catalyst-design-guided development of new reactions, privileged cinchona alkaloid-derived betaine catalysts have been successfully applied to an asymmetric Mannich reaction between the deconjugated γ- substituted butenolides and the cyclic α-ketimine esters, generating precursors of versatile α,α-disubstituted amino acids bearing two noncontinuous stereocenters with excellent chemo-, regio-, diastereo- and enantioselectivities (up to 99% ee and 90:10 dr) by altering betaine’s inherent powerful ability to promote proton transfer. Notably, this Mannich reaction also exhibited unique α-addition of butenolides and a great tolerance of functional groups on ketimines which are rarely reported.