Exploration of New C−O Electrophiles in Cross-Coupling Reactions

Abstract

Since their development in the 1970s, cross-coupling reactions catalyzed by transition metals have become one of the most important tools for constructing both carbon-carbon and carbon-heteroatom bonds. Traditionally, organohalides were widely studied and broadly used as the electrophile, both in the laboratory and in industry. Unfortunately, the high cost, environmental toxicity, and sluggish preparation often associated with aryl halides can make them undesirable for the large-scale syntheses of industrial applications. However, with the further development of catalytic systems, and particularly of the ligands contained therein, a variety of electrophiles have now been successfully applied to cross-coupling reactions. Oxygen-based electrophiles have attracted much attention due to their ready availability from phenol and carbonyl compounds. Initially, aryl and alkenyl triflates were used in cross-coupling reactions due to their high reactivity; however, low moisture stability and high cost hampered their application. Later, with the development of highly efficient catalytic systems, the less reactive sulfonates and phosphates were successfully employed in cross-coupling reactions. Although they have higher stability and can be easily prepared, low atom economy remains an obstacle to their broader utility. Our group has worked to directly apply the abundant and readily available oxygen-containing compounds, such as phenols, alcohols, ethers, and carbonyl compounds, to cross-coupling reactions. In this Account, we describe our recent efforts in transition-metal-catalyzed cross-coupling reactions of new O-based electrophiles via C-O bond activation. We began by developing the methylation of aryl methyl ethers and benzyl methyl ethers via Ni-catalyzed selective C-O bond cleavage. With the refined Ni-based catalytic system, we further applied aryl/alkenyl carboxylates and carbamates to Suzuki-Miyaura, Negishi, and Kumada-Tamao-Corriu reactions to construct various biaryl scaffolds and highly substituted alkenes. To further improve the carbon atom economy, we developed the diaryl sulfates as one-by-one electrophiles (that is, both aryl groups are used in the reaction). Most recently, we have achieved the first successful cross-coupling reaction of magnesium naphtholates with aryl Grignard reagents. These results extend aryl and benzyl ethers, aryl and alkenyl carboxylates/carbamates, and magnesium naphtholates as novel electrophiles in cross-coupling reactions. More importantly, these studies contribute to our better understanding the intrinsic nature of C-O bonds, which were traditionally considered "inert" but clearly show enormous synthetic potential with the proper catalysts.

Group Exchange between Ketones and Carboxylic Acids through Directing Group Assisted Rh-Catalyzed Reorganization of Carbon Skeletons

“…Various functionalities, including PhO-(3c), AcO-(3d), and different halides (3e−g), survived well, providing opportunities for further functionalization. 15 The steric hindrance obviously decreased the efficiency although ortho-methoxylbenzoic acid (3p) showed the credible efficiency. Notably, heteroaromatic carboxylic acids, such as 2-thienylcarboxylic acid (3t) and 2-furic acid (3u), showed the acceptable reactivity and the desired products were isolated in good yields.…”

Nickel‐Catalyzed Enantioselective CC Bond Formation through CO Cleavage in Aryl Esters

“…[2,3] Despite the advances realized, [1] the development of asymmetric CÀO bond cleavage reactions using ester derivatives remains largely undeveloped. In recent years, elegant stereoselective transformations have recently been reported by the groups of Jarvo [4] and Watson [5] (Scheme 1, path a) using ester counterparts; unfortunately, these methods are restricted to the formation of tertiary stereocenters, requiring the installation of a preexisting stereogenic center.…”

“…[1] Such popularity is largely due to the availability and lack of toxicity of phenols compared to organic halides, representing a significant step forward for their utilization in cross-coupling techniques. Among the phenol series, the utilization of aryl sulfonates, particularly aryl triflates, has become routine due to their high reactivity, low barrier for C À O oxidative addition, and the lack of regioselectivity issues for CÀO bond cleavage (Scheme 1, top left).…”

Metal catalyzed cross-coupling of aryl and benzyl methyl sulfides: nickel catalyzed Caryl–Csp3 and Csp3–Csp3 bond formations

“…Anisole derivatives are a good example for such a limitation: although they are naturally available in a wide variety and thereby ecologically and economically interesting electrophiles for cross-coupling reactions, the dealkoxylative C-C bond forming cross-coupling of anisoles is limited to few transformations. [2][3][4][5] In context of a recent natural product synthesis we envisioned a two-step process and developed a synthetic concept to enable diversification of unreactive anisole derivatives. 5 During those studies the functionalization of unreactive aryl methyl sulfides (Scheme 1) caught our interest, since the replacement of the SMe group with an activated carbon atom would give access to a variety of products including olefins, 6 various alcohols, 7 and amines, 8 diols, 9 and aromatic carboxylic acids 10 among others.…”