无过渡金属及无碱参与的N-苄基-N-叔丁基羰基酰胺的转酰胺化

Transamidation of N-Benzyl-N-Boc-amides under Transition Metal-Free and Base-Free Conditions

报道了一种无过渡金属和无碱条件下N-苄基-N-叔丁基羰基酰胺发生转酰胺化的方法.该反应从高活性的N-叔丁基羰基酰亚胺出发,历经亲核取代机理,可以中等到优良的收率得到一系列取代酰胺产物.值得一提的是,由于反应体系无需添加额外的碱,使得氨基酸衍生的手性亲核试剂及具有手性碳的酰胺在反应过程中其手性均能得到保持.此外,应用该方法还合成得到一些前药及抗抑郁症药物吗氯贝胺,展示了该方法在有机合成中的潜在应用.

A new protocol for the transamidation of N-benzyl-N-Boc-amides under transition metal-free and base-free conditions is described.The reaction features high reactivity of N-Boc-imides via direct acyl nucleophilic substitution mechanism,and provides access to a diverse array of substituted amides in good to excellent yields.Notably,the base-free condition preserves enantiopurity with respect to chiral amino-acid-derived nucleophiles,and N-Boc-amides bearing an epimerizable stereocenter.The application of this method is also demonstrated through the synthesis of pro-drugs and antidepressant moclobemide.