Huang Mingming, Sun Huaxing, Seufert Florian, Friedrich Alexandra, Marder Todd B, Hu Jiefeng
Institut für Anorganische Chemie and Institute for Sustainable Chemistry & Catalysis with Boron, Julius-Maximilians-Universität Würzburg, Am Hubland, 97074, Würzburg, Germany.
State Key Laboratory of Organic Electronics and Information Displays & & Institute of Advanced Materials (IAM), College of Chemistry and Life Sciences, Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing, 210023, China.
Angew Chem Int Ed Engl. 2024 Aug 12;63(33):e202401782. doi: 10.1002/anie.202401782. Epub 2024 Jul 17.
gem-Diborylalkanes are highly valuable building blocks in organic synthesis and pharmaceutical chemistry due to their ability to participate in multi-step cross-coupling transformations, allowing for the rapid generation of molecular complexity. While progress has been made in their synthetic metholodology, the construction of β-tertiary and C(sp)-rich gem-diborylalkanes remains a synthetic challenge due to substrate limitations and steric hindrance issues. An approach is presented that utilizes synergistic photoredox and copper catalysis to achieve efficient C(sp)-C(sp) cross-coupling of alkyl N-hydroxyphthalimide esters, which can easily be obtained from alkyl carboxylic acids, with diborylmethyl species, providing a series of C(sp)-rich gem-diborylalkanes with 1°, 2°, and even 3° β positions. Furthermore, this approach can also be applied to complex medicinal compounds and natural products, offering rapid access to molecular complexity and late-stage functionalization of C(sp)-rich drug candidates. Mechanistic experiments revealed that diborylmethyl Cu(I) species participated in both the photoredox process and the key C(sp)-C(sp) bond-forming step.
偕二硼基烷烃是有机合成和药物化学中非常有价值的结构单元，因为它们能够参与多步交叉偶联转化，从而能够快速生成分子复杂性。虽然它们的合成方法已经取得了进展，但由于底物限制和空间位阻问题，构建β-叔碳和富含C(sp)的偕二硼基烷烃仍然是一个合成挑战。本文提出了一种利用光氧化还原和铜催化协同作用的方法，以实现烷基N-羟基邻苯二甲酰亚胺酯（可容易地从烷基羧酸获得）与二硼基甲基物种的高效C(sp)-C(sp)交叉偶联，提供一系列具有1°、2°甚至3°β位的富含C(sp)的偕二硼基烷烃。此外，该方法还可应用于复杂的药物化合物和天然产物，能够快速实现分子复杂性以及富含C(sp)的候选药物的后期官能化。机理实验表明，二硼基甲基铜(I)物种参与了光氧化还原过程和关键的C(sp)-C(sp)键形成步骤。
