Gabbey Alexis L, Michel Nicholas W M, Hughes Jonathan M E, Campeau Louis-Charles, Rousseaux Sophie A L
Davenport Research Laboratories, Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada.
Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Org Lett. 2022 May 6;24(17):3173-3178. doi: 10.1021/acs.orglett.2c00918. Epub 2022 Apr 26.
The transition-metal-catalyzed α-arylation of secondary amides remains a synthetic challenge due to the presence of a free N-H bond. We report a strategy to synthesize secondary α-aryl amides via a Ni-catalyzed reductive arylation of redox-active -hydroxyphthalimide (NHP) esters of malonic acid half amides. This transformation proceeds under mild conditions and displays excellent chemoselectivity for amide α-arylation in the presence of other enolizable carbonyls. The NHP ester substrates are readily prepared from Meldrum's acid.
由于存在游离的N-H键，过渡金属催化的仲酰胺α-芳基化仍然是一个合成挑战。我们报道了一种通过镍催化丙二酸半酰胺的氧化还原活性α-羟基邻苯二甲酰亚胺（NHP）酯的还原芳基化来合成仲α-芳基酰胺的策略。这种转化在温和条件下进行，并且在存在其他可烯醇化羰基的情况下对酰胺α-芳基化表现出优异的化学选择性。NHP酯底物很容易由丙二酸亚异丙酯制备。
