Concise practical avenues toward 5,5-spiro-α-prolines†

Abstract

This article describes concise and practical synthetic approaches toward the multigram-scale preparation of value-added conformationally constrained 5-spirocyclic α-prolines from readily accessible starting materials. Direct carboxylation of 2-spiropyrrolidines is a novel and promising approach to achieve this goal, particularly for substrates with no acidic centers within the spiro-linked portion of the pyrrolidine core. The method allows for quick, one-step preparation of the target chemicals in good yields. An alternative synthetic avenue was designed for substrates unsuitable for direct carboxylation. This 4-step protocol involves common laboratory practice transformations and is comparable in its efficiency to the carboxylation method. This study concludes a series of our investigations on the elaboration of efficient methods for the construction of spiro-proline frameworks.