Asymmetric synthesis of dihydro-1,3-dioxepines by Rh(ii)/Sm(iii) relay catalytic three-component tandem [4+3]-cycloaddition

Heterocycles have been widely used in organic synthesis, agrochemical, pharmaceutical and materials science industries. Catalytic three-component ylide formation/cycloaddition enables the assembly of complex heterocycles from simple starting materials in a highly efficient manner. However, asymmetric versions remain a yet-unsolved task. Here, we present a new bimetallic catalytic system for tackling this challenge. A combined system of Rh(ii) salt and chiral N,N ' -dioxide-Sm(iii) complex was established for promoting the unprecedented tandem carbonyl ylide formation/asymmetric [4 + 3]-cycloaddition of aldehydes and alpha -diazoacetates with beta,gamma -unsaturated alpha -ketoesters smoothly, affording various chiral 4,5-dihydro-1,3-dioxepines in up to 97% yield, with 99% ee. The utility of the current method was demonstrated by conversion of products to optically active multi-substituted tetrahydrofuran derivatives. A possible reaction mechanism was provided to elucidate the origin of chiral induction based on experimental studies and X-ray structures of catalysts and products.

Automated summary

A new bimetallic catalytic system was established for efficient synthesis of chiral heterocycles. The system promoted asymmetric [4 + 3]-cycloaddition reaction, leading to various chiral 4,5-dihydro-1,3-dioxepines in yields up to 97% with 99% ee.