Chapter 38: Synthesis and Reactions of Carbenes

Carbenes exist in two distinct electronic states: the singlet state, where both non-bonding electrons occupy the same orbital with paired spins, and the triplet state, where the electrons occupy separate orbitals with parallel spins. The singlet form is typically more reactive and selective in synthetic applications, while the triplet form exhibits different reactivity and requires special handling. The chapter details multiple methods for generating carbenes in situ, including decomposition of diazo compounds through thermal activation or photolysis, which release nitrogen gas and form highly reactive carbene intermediates. An important class of synthetic carbenes involves dichlorocarbene, generated from chloroform and strong base, which participates in characteristic addition reactions to alkenes. The chapter emphasizes the Simmons-Smith reaction, a practical and widely used method for generating a carbenoid reagent from diiodomethane and zinc, which allows controlled cyclopropanation of alkenes with high stereoselectivity and without rearrangement. Beyond addition reactions, the chapter explores carbene insertion reactions, where carbenes insert into carbon-hydrogen and carbon-heteroatom bonds, and discusses the stereochemical outcomes that result from the electronic nature of carbene intermediates. The stability and reactivity of carbenes depend heavily on substituents; electron-donating groups stabilize carbenes while electron-withdrawing groups destabilize them. Wolf rearrangement and related transformations demonstrate how carbenes derived from diazo compounds can undergo rearrangement under specific conditions. Throughout the chapter, strategic considerations for carbene chemistry in synthesis are emphasized, including chemoselectivity, regioselectivity, and the importance of controlling singlet versus triplet carbene formation to achieve desired products. The chapter concludes by demonstrating how carbene chemistry has become an indispensable tool in modern organic synthesis for creating three-membered rings and for executing complex molecular transformations.