We report the first example of a catalytic asymmetric reductive amination under dynamic kinetic resolution (DKR) conditions for the preparation of a chiral amine as a key intermediate toward Tofacitinib, an active pharmaceutical ingredient developed by Pfizer. Such a protocol allows the preferential formation of a single product out of four possible diastereomers of the chiral amine starting from the corresponding racemic ketone. The chiral iridium catalyst able to perform such a feast was discovered through a mix of high-throughput screening, racemization study, and reaction optimization.

中文翻译：

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托法替尼关键中间体的不对称合成，通过动态动力学拆分-还原胺化方案进行

我们报告了在动态动力学分辨率（DKR）条件下制备手性胺作为Tofacitinib（一种由辉瑞公司开发的活性药物成分的关键中间体）的关键中间体的催化不对称还原胺化的第一个例子。这样的方案允许从相应的外消旋酮开始，从四种可能的手性胺的非对映异构体中优先形成单个产物。通过高通量筛选，外消旋研究和反应优化相结合，发现了能够进行此类盛宴的手性铱催化剂。