Design, synthesis, and evaluation of a new generation of modular nucleophilic glycine equivalents for the efficient synthesis of sterically constrained alpha-amino acids.

A new generation of modular achiral glycine equivalents have been evaluated with respect to their synthetic utility for the production of tailor-made, sterically constrained alpha-amino acids, which proved to be the most efficient approach developed to date for the synthesis of symmetrical alpha,alpha-disubstituted-alpha-amino acids. Among the new series of achiral glycine equivalents, one was found to be a superior glycine derivative for the Michael additions with various (R)- or (S)-N-(E-enoyl)-4-phenyl-1,3-oxazolidin-2-ones representing a general and practical synthesis of sterically constrained beta-substituted pyroglutamic acids. In particular, the application of these complexes allowed for the preparation of several beta-substituted pyroglutamic acids which include electron-releasing and sterically demanding substituents in the structure thus increasing the synthetic efficiency and expanding the generality of these Michael addition reactions.