Stereoselective Cycloaddition Reactions

Abstract

Cycloaddition is a member of pericyclic reactions in which reactive components possessing conjugated π‐electrons (e.g., diene/dienophile, 1,3‐dipole/dipolarophile, and ketene/imine) transform into cyclic molecules. These reactions proceed in a concerted mechanism with a high degree of regio‐ and stereoselectivity. Thus, they have been widely used for the construction of cyclic skeletons of numerous natural products and pharmacologically active molecules. Based on the π‐electron systems of reactants, they can be further classified into [4 + 2], [3 + 2], and [2 + 2] cycloadditions that produce six‐, five‐, and four‐membered rings, respectively. On the other hand, whereas natural products and designed synthetic molecules may offer a starting point in drug development, improvement of their structures and properties is frequently needed to optimize their biological efficacy. To this end, solid‐phase synthesis is a powerful tool for generating a large number of compounds with synthetic convenience and many solid‐phase cycloaddition reactions have been reported to date. This review, in particular, summarizes stereoselective cycloaddition reactions and their solid‐phase versions carried out on polymer supports for the synthesis of natural products and their analogs, focusing on the reactions that were employed as key steps.