Bai Dachang, Zhong Kangbao, Chang Lingna, Qiao Yan, Wu Fen, Xu Guiqing, Chang Junbiao
State Key Laboratory of Antiviral Drugs, NMPA Key Laboratory for Research and Evaluation of Innovative Drug, School of Chemistry and Chemical Engineering, Henan Normal University, Pingyuan laboratory, Xinxiang, 453007, China.
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032, P R China.
Nat Commun. 2024 Jul 28;15(1):6360. doi: 10.1038/s41467-024-50743-w.
The fluoroalkyl-containing organic molecules are widely used in drug discovery and material science. Herein, we report ligand regulated nickel(0)-catalyzed regiodivergent hydrosilylation of α-(fluoroalkyl)styrenes without defluorination, providing an atom- and step-economical synthesis route of two types of fluoroalkyl substituted silanes with exclusive regioselectivity. The anti-Markovnikov addition products (β-fluoroalkyl substituted silanes) are formed with monodentate phosphine ligand. Noteworthy, the bidentate phosphine ligand promote the generation of the more challenging Markovnikov products (α-fluoroalkyl substituted silanes) with tetrasubstituted saturated carbon centers. This protocol features with easy available starting materials and commercially available nickel catalysis, a wide range of substrates and excellent regioselectivity. The structure divergent products undergo a variety of transformations. Comprehensive mechanistic studies including the inverse kinetic isotope effects demonstrate the regioselectivity controlled by ligand structure through α-CF nickel intermediate. DFT calculations reveal a distinctive mechanism involving an open-shell singlet state, which is crucial for generating intricate tetra-substituted Markovnikov products.
含氟烷基的有机分子在药物发现和材料科学中广泛应用。在此，我们报道了配体调控的零价镍催化的α-（氟烷基）苯乙烯的区域发散性硅氢化反应，该反应不发生脱氟，提供了一种原子经济性和步骤经济性的合成路线，可选择性地合成两种具有区域选择性的氟烷基取代硅烷。单齿膦配体可形成反马氏加成产物（β-氟烷基取代硅烷）。值得注意的是，双齿膦配体促进生成更具挑战性的马氏产物（α-氟烷基取代硅烷），其具有四取代的饱和碳中心。该方法具有起始原料易得、镍催化剂可商购、底物范围广和区域选择性优异等特点。结构不同的产物可进行多种转化。包括逆动力学同位素效应在内的全面机理研究表明，区域选择性由配体结构通过α-CF镍中间体控制。密度泛函理论计算揭示了一种独特的机理，涉及开壳单重态，这对于生成复杂的四取代马氏产物至关重要。
