Multigram Synthesis of 3,3-Spiro-α-prolines

Abstract

A series of novel spirocyclic α-proline building blocks with a spiro conjunction in position 3 of the pyrrolidine ring was prepared to employ two convenient and practical synthetic approaches. Both alternative routes utilize simple and readily available starting materials─cyclic ketones and esters─and comprise 6 and 7 steps, respectively. The methodologies feature distinct advantages, using routine organic chemistry transformations, and are suitable for producing multigram amounts of the target prolines. The approach also became valuable for spirocyclic pyroglutamic acids.