Systematic Evaluation of 1,2-Migratory Aptitude in Alkylidene Carbenes

Abstract

Alkylidene carbenes undergo rapid inter- and intramolecular reactions and rearrangements, including 1,2-migrations of β-substituents to generate alkynes. Their propensity for substituent migration exerts profound influence over the broader utility of alkylidene carbene intermediates, yet prior efforts to categorize 1,2-migratory aptitude in these elusive species have been hampered by disparate modes of carbene generation, ultrashort carbene lifetimes, mechanistic ambiguities, and the need to individually prepare a series of ¹³C-labeled precursors. Herein we report on the rearrangement of ¹³C-alkylidene carbenes generated <i>in situ</i> by the homologation of carbonyl compounds with [¹³C]-Li-TMS-diazomethane, an approach that obviates the need for isotopically labeled substrates and has expedited a systematic investigation (¹³C{¹H} NMR, DLPNO-CCSD(T)) of migratory aptitudes in an unprecedented range of more than 30 alkylidene carbenes. Hammett analyses of the reactions of 26 differentially substituted benzophenones reveal several counterintuitive features of 1,2-migration in alkylidene carbenes that may prove of utility in the study and synthetic application of unsaturated carbenes more generally.