Ligand‐Controlled C−O Bond Coupling of Carboxylic Acids and Aryl Iodides: Experimental and Computational Insights

Abstract

Palladium‐catalyzed cross‐coupling reactions between carboxylic acids and aryl halides have several possible competitive pathways. Decarboxylative C−C bond coupling and C−H arylation are well established in the literature. However, direct C−O bond coupling between carboxylic acids and aryl halides has received little success. In this report, we describe a protocol for exclusive C−O bond formation, enabled by a bidentate N,N‐ligand such as 1,10‐phenanthroline. The reaction is general for a broad range of carboxylic acids and iodoarenes. Experimental evidence and computational results suggest a high energy barrier for the alternative pathway of decarboxylative carbon‐carbon bond coupling.

Development of copper-catalyzed deaminative esterification using high-throughput experimentation

“…4). Aliphatic (17,24,36), benzylic (23,32,37), and aromatic (6,27,35) carboxylic acids performed well giving desired products in 48-89% isolated yield. Amino acids were viable substrates, with both N-Boc (7) and N-tosyl proline (31) generating the desired ester product (8,24) in good yield.…”

“…A variety of functionalities were tolerated such as N-Boc groups (5,20,3,4), N-toluenesulfonamides (18,31), nitro-( 27), thiazolo- (30), fluoro- (23), and styrenyl motifs (25). Diazonium salts derived from both electron-rich (6,16,19,38) and electron- deficient (21,26,28) aryl amines were successful giving desired products in 64-89% yield. Sterically hindered diazonium salts were also viable (34).…”

“…Esters are one of the most prevalent functional groups among natural and industrial chemicals. Their synthesis has classically relied on Fischer's esterification method to unite alcohol and an acid 5 , although complementary esterification reactions of acids with aryl halides [6][7][8][9] , aryl boronates [10][11][12] , aryl sulfonates 13 , aryl iodonium salts 14,15 and silanes 16 have emerged. An amine-acid esterification would leverage the abundance of two popular building blocks (Fig.…”

Exogenous Ligand‐Free Nickel‐Catalyzed Carboxylate O‐Arylation: Insight into NiI/NiIII Cycles**

“…Aryl halides lacking sufficient electron-withdrawing groups show low reactivity (8, 9, 10) presumably because of a slow rate for oxidative addition. A variety of electron-poor aryl bromides were found to be effective coupling partners (11)(12)(13)(14)(15). For the carboxylic acid coupling partner, sterically hindered pivalic acid and cyclohexanecarboxylic acid (16,17) furnished the corresponding ester efficiently, as well as various aromatic carboxylic acids (19)(20)(21).…”

“…Although analogous O-aryl ester bond formation reactions catalyzed by palladium have been reported, these protocols are far from mild and efficient, and are relying on stoichiometric amounts of silver salts. [11,12] Mechanistically, nickel-catalyzed CÀ heteroatom bond formations under thermal conditions were proposed to proceed via a self-sustained Ni I / Ni III catalytic cycle. [10] In addition, the relevance of this catalytic mechanism was also demonstrated under photochemical [13][14][15][16][17] and electrochemical [14] reaction conditions.…”