Harnessing carbene polarity: Unified catalytic access to donor, neutral, and acceptor carbenes
Khue N. M. Nguyen, Xueling Mo, Bethany M. DeMuynck, Mohamed Elsayed, Jacob J. A. Garwood, Duong T. Ngo, Ilias Khan Rana, David A. Nagib
Abstract
Metal carbenes are highly useful intermediates in organic synthesis. However, not all classes of carbene polarity are catalytically accessible, nor are there common precursors known to synthesize all of these electronically diverse carbene types. Here, we report a unified strategy to access a full range of carbenes, including those with donor substituents (EDG: OMe, NR 2 , alkyl), acceptor substituents (EWG: CN, CO 2 R), and electronically neutral or nonpolar substituents (H, BR 2 , SiR 3 , halide, aryl, heteroaryl). This Fe-catalyzed method harnesses α-Cl radicals and couples an exceptionally wide array of carbenes in (2+1) cyclopropanations and σ-bond insertions. This mild, robust, and electronically tunable synthetic method facilitated the development of a better classification system for catalytic metal carbenes (validated by both kinetic and thermodynamic quantification), as well as a carbene “click-like” reaction and aqueous adaptation for chemical biology applications.