Diversity by Divergence: Solution-Phase Parallel Synthesis of a Library of N-Diversified 1-Oxa-7-Azaspiro[4.5]decan-2-yl-Propanes and -Butanes

Abstract

The synthesis of a 162-member compound library derived from a single precursor via a multistage divergence strategy is described. Divergence is sequentially introduced in three ways: (1) by early preparation of two separable spirocyclic diastereomers, (2) by elaboration of each spirocyclic diastereomer to a different scaffold using four Horner-Emmons-Wadsworth reagents, and (3) by employing three different modes of nitrogen diversification with each scaffold to afford the final compounds. This 2 diastereomers × 4 reagents × 3 modes of diversification strategy leads to 24 unique synthetic pathways that ultimately afforded, in parallel format, the 162-compound set.