Phosphine-mediated Highly Enantioselective Spirocyclization with Ketimines as Substrates

Abstract

Phosphine-catalyzed enantioselective annulation reactions involving ketimines are a daunting synthetic challenge owing to the intrinsic low reactivity of ketimine substrates. A highly enantioselective [3+2] cycloaddition reaction that makes use of isatin-derived ketimines as reaction partners was developed. Notably, both simple and γ-substituted allenoates could be utilized, and various 3,2'-pyrrolidinyl spirooxindoles with a tetrasubstituted stereocenter were obtained in excellent yields and with nearly perfect enantioselectivity (>98 % ee in all cases).

Keywords: [3+2] cycloaddition; acyclic ketimines; amino acids; phosphine catalysts; spirooxindoles.