Carbonyl desaturation is a fundamental reaction widely practised in organic synthesis. While numerous methods have been developed to expand the scope of this important transformation, most of them necessitate multi-step protocols or suffer from the use of high loadings of metal or strong oxidizing conditions. Moreover, approaches that can achieve precise stereochemical control of the desaturation process are extremely rare. Here we report a biocatalytic platform for desymmetrizing desaturation of cyclohexanones to generate diverse cyclohexenones bearing a remote quaternary stereogenic centre, by reengineering ‘ene’-reductases to efficiently mediate dehydrogenation, the reverse process of their native activity. This ‘ene’-reductase-based desaturation system operates under mild conditions with air as the terminal oxidant, tolerates oxidation-sensitive or metal-incompatible functional groups and, more importantly, exhibits unparalleled stereoselectivity compared with those achieved with small-molecule catalysts. Mechanistic investigations suggest that the reaction proceeded through α-deprotonation followed by a rate-determining β-hydride transfer.

羰基去饱和是有机合成中广泛使用的基本反应。虽然已经开发了许多方法来扩大这一重要转变的范围，但其中大多数方法都需要多步骤方案，或者受到使用高金属负载或强氧化条件的影响。此外，能够实现去饱和过程的精确立体化学控制的方法极为罕见。在这里，我们报道了一个生物催化平台，该平台通过重新设计“烯”还原酶来有效介导脱氢，即其天然活性的相反过程，从而产生带有远程四元立体中心的环己酮去对称化，以产生带有远程四元立体中心的多样化环己酮。这种基于“烯”还原酶的去饱和系统在温和的条件下运行，以空气为末端氧化剂，可耐受氧化敏感或金属不相容的官能团，更重要的是，与小分子催化剂相比，它表现出无与伦比的立体选择性。机理研究表明，反应通过 α-deprotonation 进行，然后是速率确定的 β-氢化物转移。