Tan Zhenda, Liu Yangbin, Feng Xiaoming
Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen 518132, China.
Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, China.
Sci Adv. 2024 Jun 7;10(23):eadn9738. doi: 10.1126/sciadv.adn9738. Epub 2024 Jun 5.
α-Chiral alkyl phosphines are privileged structural motifs with a wide application in organic and medical synthesis. It is highly desirable to develop stereoselective methods to prepare these enantioenriched molecules. The incorporation of C()─H functionalization and chiral phosphine chemistry is much less explored, probably because of the weak reactivity of C()─H bonds and/or the challenging site- and stereoselectivity issues. Herein, we disclose a synergistic catalysis system to enable an enantioselective radical addition process of α-substituted vinylphosphine oxides. An array of diverse α-chiral alkyl phosphors compounds is smoothly accessed by using the readily available chemicals as the inert C()─H bond reagent, such as sulfides, amines, alkenes, and toluene derivatives, exerting remarkable chemo-, site-, and enantioselectivity. On the basis of the mechanistic studies, both the C()─H bond activation and the stereochemistry-determining step are proposed to involve a single-electron transfer/proton transfer process.
α-手性烷基膦是一类重要的结构单元，在有机合成和药物合成中有着广泛的应用。开发立体选择性方法来制备这些对映体富集的分子是非常有必要的。碳氢键官能化与手性膦化学的结合研究较少，这可能是由于碳氢键的反应活性较弱和/或位点及立体选择性问题具有挑战性。在此，我们报道了一种协同催化体系，可实现α-取代乙烯基氧化膦的对映选择性自由基加成反应。使用易得的化学品作为惰性碳氢键试剂，如硫化物、胺、烯烃和甲苯衍生物，可以顺利合成一系列多样的α-手性烷基膦化合物，该反应具有显著的化学、位点和对映选择性。基于机理研究，碳氢键活化和立体化学决定步骤均被认为涉及单电子转移/质子转移过程。
