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Cleary, Sarah E.; Hensinger, Magenta J.; Qin, Zhi-Xin; Hong, Xin; Brewer, Matthias (, The Journal of Organic Chemistry)
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Liu, Chengwei; Qin, Zhi-Xin; Ji, Chong-Lei; Hong, Xin; Szostak, Michal (, Chemical Science)Aryl carboxylic acids are among the most abundant substrates in chemical synthesis and represent a perfect example of a traceless directing group that is central to many processes in the preparation of pharmaceuticals, natural products and polymers. Herein, we describe a highly selective method for the direct step-down reduction of carboxylic acids to arenes, proceeding via well-defined Pd(0)/( ii ) catalytic cycle. The method shows a remarkably broad substrate scope, enabling to direct the classical acyl reduction towards selective decarbonylation by a redox-neutral mechanism. The utility of this reaction is highlighted in the direct defunctionalization of pharmaceuticals and natural products, and further emphasized in a range of traceless processes using removable carboxylic acids under mild, redox-neutral conditions orthogonal to protodecarboxylation. Extensive DFT computations were conducted to demonstrate preferred selectivity for the reversible oxidative addition and indicated that a versatile hydrogen atom transfer (HAT) pathway is operable.more » « less
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