镍催化烷基羧酸与对甲苯磺酸甲酯还原偶联甲基化成酮反应

Nickel-Catalyzed Reductive Methylation of Alkyl Acid with Methyl p-Tosylate

甲基是最小的含碳取代基团,在化合物中起到重要的作用.羧酸转化为酮是有机化学的基础反应,这种官能团变化通常是间接地将羧酸先转化为酰氯或者Weinreb酰胺再由有机金属试剂进行亲核进攻.直接将羧酸转变为酮,需要至少2 equiv.锂试剂,同时反应需要在低温下进行,往往伴随着很多叔醇的副产物.报道了利用镍催化还原偶联的方法,将有机羧酸与对甲苯磺酸甲酯进行还原偶联,一步反应直接由羧酸甲基化成酮,其特点是原料易得,反应条件温和,可以得到中等的收率并且有较好的底物适应性.

Methyl group is the smallest carbon substituent that plays important roles in many compounds. Conversion of a carboxylic acid into a ketone is a fundamental transformation in organic chemistry. This functional group change is usually performed indirectly by activating the carboxylic acid into an acyl chloride or into a Weinreb amide, and then by nucleophilic attack with an organometallic reagent. However, direct conversion of a carboxylic acid into a ketone can be achieved in one-step reaction using at least 2 equiv. of an organolithium reagent at low temperature and producing much tertiary alcohol.Herein, methylation of alkyl acid under Ni-catalyzed reductive coupling conditions using methyl p-methyl tosylate as the methylation reagent was reported to yield methylated ketones. Moderate yields as well as good functional group tolerance were observed under the present mild and easy-to-operate reaction conditions.