Catalytic Homologation Of Cycloalkanones With Substituted Diazomethanes. Mild And Efficient Single-step Access To α-tertiary And α-quaternarycarbonyl Compounds

摘要

The homologation of cyclic ketones with diazoalkanes is a strategically useful ring expansion, with origins dating back to the early twentieth century. Scheme 1 (1 + 2→4) shows the widely accepted mechanism for carbon insertion involving (1) nucleophilic attack by the diazoalkyl carbon on the carbonyl group to form a tetrahedral intermediate (diazonium betaine) and (2) 1,2-C-C bond migration with concerted loss of dinitrogen. Water and alcohol additives have long enhanced the efficiency and utility of this process, whereby protonation of the oxyanion (3, LA = H~+) in the transition state for rate-determining diazoalkyl addition can serve to discourage its collapse to epoxide byproducts. Other Lewis acids, namely BF_3 and AlCl_3, are also known to promote carbon insertion. Decomposition of the nucleophile, however, is a competitive problem when using these and other agents. Indeed, nearly all documented examples rely on superstoichiometric amounts of both diazoalkane and promoter (or methanol as cosolvent), affording low yields of product and, in the case of reactive substrates, mixtures derived from multiple homologation.