Use of Strain-Release for the Diastereoselective Construction of Quaternary Carbon Centers

Herein, we describe the formation of quaternary carbon centers with excellent diastereoselectivity via a strain-release protocol. An organometallic species is generated by Cp*Rh(III)-catalyzed C-H activation, which is then coupled with strained bicyclobutanes (BCBs) and a prochiral carbon electrophile in a three-component reaction. This work illustrates a rare example of BCBs in transition metal catalysis and demonstrates their broad potential to access novel reaction pathways. The method developed exhibits ample functional group tolerance, and the products can be further transformed into valuable alpha-quaternary beta-lactones. Preliminary mechanistic investigations suggest a twofold C-C bond cleavage sequence involving sigma-bond insertion and an ensuing beta-carbon elimination event.

Automated summary

This study describes the formation of quaternary carbon centers with excellent diastereoselectivity via a strain-release protocol, involving Cp*Rh(III)-catalyzed C-H activation to generate an organometallic species for coupling with strained bicyclobutanes and a prochiral carbon electrophile. The method demonstrates the broad potential of BCBs in transition metal catalysis and exhibits ample functional group tolerance, with products convertible into valuable alpha-quaternary beta-lactones. Preliminary mechanistic investigations suggest a twofold C-C bond cleavage sequence involving sigma-bond insertion and beta-carbon elimination.