Advances in organocatalytic asymmetric [3 + 3] cycloadditions: synthesis of chiral six-membered (hetero)cyclic compounds

Abstract

Organocatalytic asymmetric [3 + 3] cycloaddition underpins the efficient synthesis of chiral six-membered (hetero)cyclic compounds. Various elegant works were exploited to promote the prosperity of this cycloaddition-based methodology in past decades. The advantage of this unique strategy lies in great compatibility with flexible catalytic modes and multiple three-atom building blocks. This review summarizes the development of organocatalytic asymmetric [3 + 3] cycloaddition over the past twenty years. Both mechanistic studies and the activation mode of various organocatalytic systems, including (1) chiral amine catalysis, (2) chiral bifunctional catalyst catalysis, (3) chiral N-heterocyclic carbene catalysis, (4) chiral phosphoric acid catalysis, and (5) other asymmetric organocatalysis (isothioureas, phosphine and cooperative catalysis) are discussed in this review. Additionally, for each catalytic pattern, three-atom building blocks for organocatalytic asymmetric [3 + 3] cycloaddition were classified as all-carbon three-atom, aza-three-atom, oxa-three-atom building blocks and those containing other heteroatoms. This review has not only given a systematic summary of this topic, but also provided insights into the remaining challenges, which will promote the future development of this field.