Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University, 610064, Chengdu, P. R. China.
School of Pharmacy, Southwest Medical University, 646000, Luzhou, P. R. China.
Nat Commun. 2019 Aug 9;10(1):3592. doi: 10.1038/s41467-019-11528-8.
Catalytic difunctionalization of alkenes has been an ideal strategy to generate structurally complex molecules with diverse substitution patterns. Although both phosphonyl and carboxyl groups are valuable functional groups, the simultaneous incorporation of them via catalytic difunctionalization of alkenes, ideally from abundant, inexpensive and easy-to-handle raw materials, has not been realized. Herein, we report the phosphonocarboxylation of alkenes with CO via visible-light photoredox catalysis. This strategy is sustainable, general and practical, providing facile access to important β-phosphono carboxylic acids, including structurally complex unnatural α-amino acids. Diverse alkenes, including enamides, styrenes, enolsilanes and acrylates, undergo such reactions efficiently under mild reaction conditions. Moreover, this method represents a rare example of redox-neutral difunctionalization of alkenes with H-P(O) compounds, including diaryl- and dialkyl- phosphine oxides and phosphites. Importantly, these transition-metal-free reactions also feature low catalyst loading, high regio- and chemo-selectivities, good functional group tolerance, easy scalability and potential for product derivatization.
烯烃的双官能化反应是一种构建具有不同取代模式的结构复杂分子的理想策略。尽管膦酰基和羧基都是有价值的官能团，但通过烯烃的催化双官能化反应将它们同时引入，理想情况下是使用丰富、廉价且易于处理的原料，尚未实现。在此，我们通过可见光光氧化还原催化报告了烯烃与 CO 的膦羧化反应。该策略具有可持续性、通用性和实用性，可方便地获得重要的β-膦酸羧酸，包括结构复杂的非天然α-氨基酸。在温和的反应条件下，各种烯烃，包括烯酰胺、苯乙烯、烯醇硅烷和丙烯酸酯，都能高效地进行此类反应。此外，该方法代表了 H-P(O)化合物（包括二芳基和二烷基氧化膦和亚磷酸酯）与烯烃的氧化还原中性双官能化反应的罕见实例。重要的是，这些无过渡金属的反应还具有低催化剂负载、高区域和化学选择性、良好的官能团耐受性、易于规模化和产物衍生化的潜力。
