Diversity-Oriented Synthesis Based on the DPPP-Catalyzed Mixed Double-Michael Reactions of Electron-Deficient Acetylenes and β-Amino Alcohols

In this study, we prepared oxizolidines through 1,3-bis(diphenylphosphino)-propane (DPPP)–catalyzed mixed double-Michael reactions of β-amino alcohols with electron-deficient acetylenes. These reactions are very suitable for the diversity-oriented parallel syntheses of oxizolidines because: (i) they are performed under mild metal-free conditions and (ii) the products are isolated without complicated work-up. To demonstrate the applicability of mixed double-Michael reactions for the preparation of five-membered-ring heterocycles, we prepared 60 distinct oxazolidines from five β-amino alcohols and 12 electron-deficient acetylenes. We synthesized 36 of these 60 oxazolidines in enantiomerically pure form from proteinogenic amino acid–derived β-amino alcohols.