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

Abstract

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.

Advances in nucleophilic phosphine catalysis of alkenes, allenes, alkynes, and MBHADs

“…Kwon and Sriramurthy reported the first examples of mixed double-Michael reactions, allowing access to highly functionalized oxazolidines, thiazolidines, and pyrrolidines with excellent efficiencies and diastereoselectivities. 56 Using di-nucleophiles derived from L-amino acids, the annulation products were obtained in enantiomerically pure form (Scheme 63). The use of 1,3-bis(diphenylphosphino)propane is critical, providing anchimeric assistance in stabilizing the reaction intermediates.…”

Organocatalytic transformations of alkynals, alkynones, propriolates, and related electron-deficient alkynes

“…In 2011, the same authors expanded the scope of this methodology synthesizing sixty different chiral heterocycles. 86 Using the same strategy, Kwon and co-workers have also prepared seven different types of benzannulated N-heterocycles 164 in a one-step process in excellent yields. In some cases, it was necessary to use acetic acid and sodium acetate as additives to expedite efficient proton transfer steps (Scheme 73).…”

Chiral Aminophosphines as Catalysts for Enantioselective Double-Michael Indoline Syntheses

“…In 2007, we reported a phosphine-catalyzed double-Michael addition in which a bisphosphine was the best catalyst [23-25]. We suggested that anchimeric assistance by the other tethered phosphino group stabilized the resultant phosphonium cation in the transitional intermediates, leading to a higher yield of the double-Michael adduct.…”