A simple NaOMe catalyst provides superior accessibility to a wide variety of functionalized amides including peptides through direct amination of esters in an atom-economical and environmentally benign way.

A catalytic amount of 4-dimethylaminopyridine showed drastic additive effects on transesterification catalyzed by the μ 4 -oxo-tetranuclear zinc cluster Zn 4 (OCOCF 3 ) 6 O, enhancing the catalytic activity by more than 15-fold. The new catalyst system facilitates transesterification of less reactive sterically demanding esters and alcohols.

A new catalytic deacylation of acetates and benzoates through transesterification with methanol was developed (see scheme). Reactions with various acid- and nucleophile-sensitive functional groups proceeded efficiently in the presence of a catalytic amount of the tetranuclear zinc cluster. The present catalysis is applicable to less-reactive tertiary acetates, the deacylation of which is difficult to achieve by transesterification with other catalysts.

The electronic effects of tetranuclear zinc cluster catalysts on transesterification were investigated by changing the carboxylate ligands in the clusters. High catalyst activity crucially depended on the balance between Lewis acidity and Brønsted basicity of the catalyst; this was consistent with the dual activation of both the electrophile and nucleophile by the cooperative zinc centers. In addition, tetranuclear zinc cluster catalysts achieved the transesterification of β-keto esters with unprecedented levels of broad substrate generality, in which a newly developed pentafluoropropionate-bridged zinc cluster and 4-dimethylaminopyridine additive greatly improved the reactivity of sterically congested α- and α,α-disubstituted β-keto esters.

Acylation is one of the most abundant organic transformations of alcohols (esterification) and amines (amidation). Because of the greater nucleophilicity of the amino group compared to the hydroxyl group and the stability of amides compared to esters, N-acylation occurs predominantly in organic synthetic reactions. We reported that the μ-oxo-tetranuclear zinc cluster Zn4(OCOCF3)6O efficiently catalyzes highly chemoselective acylation of hydroxyl groups in the presence of primary and secondary alkyl amino groups to afford the corresponding esters in high yields. Not only zinc carboxylate complexes but also various carboxylate complexes of first-row late transition metals, such as Mn, Fe, Co, and Cu, become catalysts for such the hydroxy group-selective acylation in the presence of amines. Among these carboxylate compounds, we found that the combination of an octanuclear cobalt carboxylate cluster [Co4(OCOR)6O]2 (R = CF3, CH3, and tBu) with nitrogen-containing ligands such as 2,2′-bipyridine show sufficient catalytic activity toward O-selective transesterification. Notably, an alkoxide-bridged dinuclear complex, Co2(OCOtBu)2(bpy)2(μ2-OCH2-C6H4-4-CH3)2, was successfully isolated as a key intermediate that proceeds with Michaelis–Menten behavior through an ordered ternary complex mechanism similar to dinuclear metallo-enzymes, suggesting that the formation of alkoxides, followed by coordination of the ester, is responsible for the unique O-selective acylation.