美国加州理工学院Gregory C. Fu和Caiyou Chen经过不懈努力，实现了铜催化的含氧亲核试剂的手性汇聚烷基化。该研究于2023年3月30日发表于国际一流学术期刊《自然》杂志上。

在该研究中，科学家使用了一个现成的铜催化剂以及含氧亲核试剂，实现了针对α-卤代酰胺的（一种有用的亲电试剂家族）一系列手性汇聚的取代反应，且该反应在各种广泛官能团的存在下可在温和条件下进行。这种催化剂不仅对含氧亲核试剂——也对含氮亲核试剂高度有效——以催化手性汇聚烷基化，这进一步支持过渡金属催化剂作为实现杂原子亲核试剂手性选择性烷基化反应挑战的解决方案。

据了解，因为碳-氧键在有机分子中极为常见，包括手性生物活性化合物，开发同时控制手性选择性的合成新方法对合成化学来说是个重要目标。Williamson醚合成——首次报道于1850年——是含氧亲核试剂烷基化的最常用方式。然而，该反应由于其反应机制（SN2反应）而具有底物范围和立体化学的种种限制。过渡金属催化的含氧亲核试剂与烷基亲电试剂的耦合有可能解决这些局限，但在控制手性选择性等方面进展非常缓慢。

附：英文原文

Title: Copper-Catalyzed Enantioconvergent Alkylation of Oxygen Nucleophiles

Author: Chen, Caiyou, Fu, Gregory C.

Issue&Volume: 2023-03-30

Abstract: Because carbon–oxygen bonds are commonplace in organic molecules, including chiral bioactive compounds, the development of new methods for their construction with simultaneous control of stereoselectivity is an important objective in synthesis. The Williamson ether synthesis, first reported in 18501, is the most widely used approach to the alkylation of an oxygen nucleophile, but it has significant limitations (scope and stereochemistry) due to its reaction mechanism (SN2 pathway). Transition-metal catalysis of the coupling of an oxygen nucleophile with an alkyl electrophile has the potential to address these limitations, but progress to date has been very limited2–7, especially with regard to controlling enantioselectivity. Herein we establish that a readily available copper catalyst can achieve an array of enantioconvergent substitution reactions of α-haloamides, a useful family of electrophiles, by oxygen nucleophiles; the reaction proceeds under mild conditions in the presence of a wide variety of functional groups. The catalyst is uniquely effective in being able to achieve enantioconvergent alkylations not only of oxygen nucleophiles, but also of nitrogen nucleophiles, furnishing support for the potential of transition-metal catalysts to provide a solution to the pivotal challenge of achieving enantioselective alkylations of heteroatom nucleophiles.

DOI: 10.1038/s41586-023-06001-y

Source: https://www.nature.com/articles/s41586-023-06001-y