Rhodium-Catalyzed One-Carbon Ring Expansion of Aziridines for the Synthesis of 2-Vinyl Azetidines

Keywords

aziridines - aziridinium ylides - ring expansion - rhodium catalysis

Significance

Methodologies for the ring expansion of aziridines are useful for accessing structural motifs that are not easily incorporated onto azetidines. This protocol utilizes the strain within the aziridine to drive the reaction forward in contrast to strain-inducing cyclization, which may be unfavorable/not observed. The introduction of the double bond provides an additional handle from which further transformations are possible. Late-stage modification of drug candidates allows for rapid expansion of the scope of structure–activity relationship studies (SARs).

Comment

This two-step protocol can be accomplished in one reaction vessel without the need for isolation of the intermediate. No cheletropic extrusion products were observed. Highly regioselective stereocontrol may be possible with the use of chiral ligands. Experimental and computational studies indicate this transformation proceeds via a diradical mechanism.

Publication History

Article published online:
28 January 2025