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5. Synthesis of biaryl ketones by arylation of Weinreb amides with functionalized Grignard reagents under thermodynamic control vs. kinetic control of N , N -Boc 2 -amides

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   A highly efficient method for chemoselective synthesis of biaryl ketones by arylation of Weinreb amides ( N -methoxy- N -methylamides) with functionalized Grignard reagents is reported. This protocol offers rapid entry to functionalized biaryl ketones after Mg/halide exchange with i-PrMgCl·LiCl under operationally-simple and practical reaction conditions. The scope of the method is highlighted in >40 examples, including bioactive compounds and pharmaceutical derivatives. Collectively, this transition-metal-free approach offers a major advantage over the recently established cross-coupling of amides by oxidative addition of N–C(O) bonds. Considering the utility of amide acylation reactions in modern synthesis, we expect that this method will be of broad interest. 

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