Palladium(II)-CataIyzed ortho Alkylation of Benzoic Acids with Alkyl Halides

摘要

The Pd~0-initiated arylation of C-H bonds with aryl halides was among the earliest examples of Pd-catalyzed C-H activation/arylation chemistry. A single pioneering example of the Pd~0-catalyzed alkylation of aryl C-H bonds using a tethered alkyl chloride was also developed by Buchwald and Hennessy for the highly efficient synthesis of oxindoles. Two examples of intra- and intermolecular alkylation of heterocycles have also been reported by Chang et al. and Hoarau et al. recently. In these reactions, no added oxidants other than the aryl halides or alkyl halides themselves are needed, which affords this C-H functionalization process a practical advantage. During the past five years, Pd~(II)-catalyzed arylation using Ar2IX as the stoichiometric oxidant through a Pd~(II)/Pd~(IV)catalytic cycle has undergone major advances. Especially noteworthy is the broad range of arylation reactions using ArI/AgOAc. To our knowledge, the Pd~(II) catalyzed intermolecular alkylation of C-H bonds with alkyl halides remains an unsolved problem, except for a single example of methylation of acetanilide with MeI. In addition, a large excess of AgOAc is required to scavenge the iodide from Pd-I species in this case. Herein we report a sequential monoselective alkylation/lactonization reaction of benzoic acids with 1,2-dichloroethane, dichloromethane, and dibromomethane (Scheme 1). Alkylation with 1-chloropen-tane was also found to proceed, albeit in lower yield. The use of alkyl chlorides instead of iodides allows the catalytic cycle to be closed in the presence of an inexpensive base without using stoichiometric amounts of Ag~+ salts.