Palladium-Catalyzed Decarboxylative Coupling of Potassium Oxalate Monoester with 2-Aryloxypyridines

Abstract

Transition metal-catalyzed C-H activation has attracted extensive attention because of its excellent functional group tolerance and high efficiency. Among them, palladium-catalyzed reactions exhibit versatile catalytic cycles and have mild conditions compared to others. Therefore, the palladium-catalyzed C-H activation has been employed broadly as a practical strategy in synthetic chemistry during the past decade. Since the first example of palladium-catalyzed decarboxylative C-H acylation using α-oxocarboxylic acids was reported in 2008, a lot of substrates have been employed to synthesize acylated products due to the easily available α-oxocarboxylic acids as well as the importance of acylation. However, the transition metal-catalyzed C-H esterification via decarbonylation is still limited. Our group previously developed the first directed C-H esterification of methyl ketoximes and 2-phenylpyridines by using potassium oxalate monoester as the decarboxylative reagent. Encouraged by this impressive result as well as the importance of salicylate derivatives in drug discovery, herein we disclose the efficient palladium-catalyzed decarboxylative esterification of 2-aryloxpyridines. This reaction proceeds smoothly with potassium oxalate monoester, affording the desired products in moderate to good yields (50%～82%). Compared to our previous work, the electron-donating pyridinyloxy (PyO) group as the directing group and six-membered metallocycle intermediate dramatically enhance the practicability and substrate tolerance of the present method. In addition, one of the products has been chosen as the model compound to deprotect the directing group to get the valuable salicylate derivative. The present method not only provides an efficient and convenient protocol for the synthesis of ethyl salicylate derivatives, but also enriches the diversity of Pd(II)/Pd(IV) catalytic reactions. A general procedure for the esterification of 2-aryloxypyridines 1 with potassium oxalate monoester 2 is as following: a mixture of 1 (0.5 mmol), Pd(OAc) 2 (10 mol%), K 2 S 2 O 8 (1.0 mmol), Ag 2 CO 3 (1.0 mmol), 2 (1.0 mmol), D-CSA (0.125 mmol), and 1,4-dioxane (2.5 mL) in a 25 mL tube was heated at 80 ℃ for a suitable time. The reaction mixture was cooled to room temperature, and concentrated in vacuo. Purification of the residue by column chromatography on silica gel with petroleum ether and ethyl acetate as the eluent provided the desired product 3.

An Efficient Metal-Free Oxidative Esterification and Amination of Benzyl C–H Bond

“…This strategy has also been successfully employed for the direct esterification and amination of C-H bonds including benzylic C-H bonds under oxidative reaction conditions. Various transition-metals efficiently catalyzed the direct esterification [7,8] and amination [9][10][11] of C-H bonds. Due to the toxicity and cost of transition-metal catalysts, increasing interest has been paid on metal-free esterifications of benzylic C-H bonds.…”

Palladium-Catalyzed ortho-C–H Alkoxycarbonylation of Aromatic Aldehydes via a Transient Directing Group Strategy

“…In this context, the development of an o -C–H alkoxycarbonylation of aromatic aldehydes is of considerable interest. For the past two decades, much progress has been made on the functionalization of C–H bonds, and some direct alkoxycarbonylation reactions of arenes based on palladium, ruthenium, or rhodium catalysis have been reported (Scheme a) . Different ester group providers, which are often toxic (diethyl azodicarboxylate), have been employed.…”

Atmosphere-Controlled Palladium-Catalyzed Divergent Decarboxylative Cyclization of 2-Iodobiphenyls and α-Oxocarboxylic Acids

“…α-Oxocarboxylic acids have emerged as one of the most versatile synthons in organic synthesis . The vast majority of efforts have been devoted to the decarboxylative acylation of several systems, such as (hetero)­aromatic rings, alkynes, alkenes, and heteroatoms, under photoredox, transition-metal, or oxidation catalysis, thus leading to the formation of C–C and C–heteroatom (N and S) bonds. , Accordingly, exploring new reaction models of α-oxocarboxylic acids is desirable. Recently, our group developed some decarboxylative cyclization reactions via a carboxyl-assisted palladacycle capture strategy .…”