Diverse Activation Modes for Ring Opening Reactions of Donor‐Acceptor Cyclopropanes

ABSTRACT

Donor–acceptor cyclopropanes (DACs) have emerged as exceptionally powerful and versatile building blocks in modern synthetic chemistry, owing to the synergistic interplay of ring strain and vicinal electronic polarization. Upon suitable activation, these strained three‐membered rings undergo selective C–C bond cleavage to generate highly reactive 1,3‐intermediates that enable rapid access to molecular complexity. While cycloaddition reactions of donor–acceptor cyclopropanes have been extensively explored and established as reliable tools for the construction of carbocycles and heterocycles, recent years have witnessed a surge of interest in nucleophilic ring‐opening reactions, particularly those leading to C–heteroatom bond formation and 1,3‐bisfunctionalization. These transformations allow the simultaneous formation of multiple bonds in single operation and provide streamlined routes to heteroatom‐rich frameworks relevant to pharmaceuticals, agrochemicals, and functional materials. This Review summarizes the advances from 2018 to the advances till date in the nucleophilic ring‐opening chemistry of donor–acceptor cyclopropanes, encompassing Lewis acid, Brønsted acid, organocatalyst, base, photoredox, and electrochemical activation modes. Emphasis is placed on mechanistic concepts, reaction design, and emerging trends that highlight donor–acceptor cyclopropanes as programmable three‐carbon synthons. By unifying diverse transformations within a common mechanistic framework, this Review aims to guide the development of new reactivity paradigms and broaden the application of donor–acceptor cyclopropanes in synthesis.