美国密歇根大学Narayan, Alison R. H.团队开发出生物催化氧化交叉偶联反应生成联芳基键。相关研究成果发表在2022年3月2日出版的国际学术期刊《自然》。
双芳基化合物具有两个相连的芳香环，广泛应用于医学、材料科学和不对称催化。为了获得这些有价值的化合物，必须加入芳烃构建块，这激发了几种形成二芳基键的方法，并向化学家提出了挑战，要求他们为该任务开发越来越简洁和可靠的方法。两个C–H键的氧化偶联为形成二芳基C–C键提供了一种有效的策略；然而，在控制将一对给定的基质结合起来的反应性和选择性方面仍然存在根本性的挑战。生物催化氧化交叉偶联反应有潜力克服许多小分子介导方法固有的局限性，提供一种催化剂控制选择性的范例。
该文中，研究人员揭示了一种利用细胞色素P450酶通过氧化C–C键形成的生物催化交叉偶联策略。研究人员证明了使用天然P450催化剂在酚类底物上催化交叉偶联反应的能力。此外，研究人员设计了一种P450，通过将低产率、非选择性反应转化为高效、选择性的过程，使其具有所需的反应性、位置选择性和atropo选择性。这种构建空间位阻二芳基键的简化方法为组装具有催化剂控制的反应性和选择性的分子提供了一个可编程的平台。
附：英文原文
Title: Biocatalytic oxidative cross-coupling reactions for biaryl bond formation
Author: Zetzsche, Lara E., Yazarians, Jessica A., Chakrabarty, Suman, Hinze, Meagan E., Murray, Lauren A. M., Lukowski, April L., Joyce, Leo A., Narayan, Alison R. H.
Issue&Volume: 2022-03-02
Abstract: Biaryl compounds, with two connected aromatic rings, are found across medicine, materials science and asymmetric catalysis1,2. The necessity of joining arene building blocks to access these valuable compounds has inspired several approaches for biaryl bond formation and challenged chemists to develop increasingly concise and robust methods for this task3. Oxidative coupling of two C–H bonds offers an efficient strategy for the formation of a biaryl C–C bond; however, fundamental challenges remain in controlling the reactivity and selectivity for uniting a given pair of substrates4,5. Biocatalytic oxidative cross-coupling reactions have the potential to overcome limitations inherent to numerous small-molecule-mediated methods by providing a paradigm with catalyst-controlled selectivity6. Here we disclose a strategy for biocatalytic cross-coupling through oxidative C–C bond formation using cytochrome P450 enzymes. We demonstrate the ability to catalyse cross-coupling reactions on a panel of phenolic substrates using natural P450 catalysts. Moreover, we engineer a P450 to possess the desired reactivity, site selectivity and atroposelectivity by transforming a low-yielding, unselective reaction into a highly efficient and selective process. This streamlined method for constructing sterically hindered biaryl bonds provides a programmable platform for assembling molecules with catalyst-controlled reactivity and selectivity.
DOI: 10.1038/s41586-021-04365-7
Source: https://www.nature.com/articles/s41586-021-04365-7