Palladium-catalyzed decarboxylative acylation of O-methyl ketoximes with a-keto acids†

Aryl ketones are important structural motifs found in natural products, medicinally relevantmolecules, and functionalmaterials. In particular, 1,2-diacylbenzenes are known to be crucial synthetic precursors to construct a wide range of biologically active compounds including phthalazines, phthalimidines, isobenzofuranes, indanones, isoindoles, and isoindolines. These facts have led to increasing interest in developing an efficient method for the preparation of 1,2-diacylbenzenes. Traditionalmetal-catalyzed crosscoupling reactions between aryl metal reagents and aryl halides are well-established methods for carbon–carbon bond formations. Recently, transition-metal-catalyzed decarboxylative cross-coupling reactions using aryl carboxylic acids as coupling partners have emerged as a promising set of carbon–carbon bond formation reactions. In these reactions, readily available carboxylic acids enable decarboxylative cross-coupling reactions to proceed with high selectivities and tolerance of functional groups. Therefore, decarboxylative cross-coupling reactions provide new alternatives for Mirozoki–Heck type reactions, oxidative arylation, redox-neutral biaryls synthesis, and allylation. Recently, directinggroup-assisted activation of aromatic ortho-C–H bonds, and subsequent acylation reaction by coupling with aldehydes or alcohols have been reported. A variety of directing groups, such as pyridines, amides, oximes, acetanilides, and indole, have been used for C–H bond activation. However, decarboxylative acylations of aromatic C–H bonds using a-keto acids as acyl surrogates were relatively unexplored. Goossen et al. first demonstrated a Pd-catalyzed decarboxylative acylation of aryl bromides with a-keto carboxylate salts as acyl anion equivalents to afford diaryl ketones. Ge et al. described palladium-catalyzed decarboxylative ortho-acylations of acetanilides and phenylpyridines with a-keto acids as acyl sources via C–H bond activation. Recently, Guo and Duan et al. reported a decarboxylative acylation of the sp C–H bond in cyclic enamides with a-keto acids. Oximes are common protection groups of the ketone moiety, and frequently used as directing groups in C–H bond activation protocols. Our continued efforts in transition-metal-catalyzed C–H bond activation and oxidative acylation reactions prompted us to explore the reaction of O-methyl ketoximes with a-keto acids. In our initial study, 4-fluoroacetophenone O-methyl oxime (1a) and phenylglyoxylic acid (2a) were chosen as model substrates for optimizing the reaction conditions, and selected results are summarized in Table 1. To our delight, the combination of Pd(OAc)2 and ammonium persulfate in DCE solvent at 70 1C can catalyze the coupling of 1a