Diastereodivergent synthesis of enantioenriched α,β-disubstituted γ-butyrolactones via cooperative N-heterocyclic carbene and Ir catalysis

Abstract

The stereodivergent synthesis of natural product frameworks via a single transformation using simple starting materials is a significant challenge. The prevalence of γ-butyrolactones in biologically active natural products has long motivated the development of enantioselective strategies towards their synthesis. Herein, we report an enantio- and diastereodivergent [3 + 2] annulation reaction for the synthesis of α,β-disubstituted γ-butyrolactones through cooperative N-heterocyclic carbene organocatalysis and iridium catalysis. This method overcomes the challenges of merging N-heterocyclic carbene organocatalysis with iridium catalysis by the appropriate choice of ligands. The use of two chiral catalysts allowed control over the relative and absolute configuration of the two formed stereocentres, thereby providing selective access to all four possible stereoisomers of the γ-lactone products. The transformation could be extended to the synthesis of δ-lactams via [4 + 2] annulation. The synthetic utility of this methodology was illustrated in the concise synthesis of the naturally occurring lignan (−)-hinokinin. Methods to allow access to all isomers of a product are both valuable and challenging to achieve. Here the authors report a catalytic system comprised of an N-heterocyclic carbene and an iridium complex, and show that it can be used for the asymmetric, diastereodivergent synthesis of γ-butyrolactones.