Ni-Catalyzed Asymmetric Hydrogenation of α-Substituted α,β-Unsaturated Phosphine Oxides/Phosphonates/Phosphoric Acids

Abstract

Efficient Ni/(S,S)-Ph-BPE-catalyzed asymmetric hydrogenation of α-substituted α,β-unsaturated phosphine oxides/phosphonates/phosphoric acids has been successfully developed, and a wide range of chiral α-substituted phosphines hydrogenation products were obtained in generally high yields with excellent enantioselective control (92%–99% yields, 84%−>99% ee). This method features a cheap transition metal nickel catalytic system, high functional group tolerance, wide substrate scope generality, and excellent enantioselectivity. A plausible catalytic cycle was proposed for this asymmetric hydrogenation according to the results of deuterium-labeling experiments.

Chiral bisphosphine Ph-BPE ligand: a rising star in asymmetric synthesis

“…In 2023, Dong et al reported the asymmetric hydrogenation of α-substituted α,β-unsaturated phosphine derivatives by using Ph-BPE and nickel catalytic system (Scheme 6e). 34 They also reported the Ni-catalyzed asymmetric hydrogenation of cyclic alkenyl sulfones with up to 99% yield and 99% ee (Scheme 6f). 35 There is a special example of constructing chiral carbons at the α-position of the double bond.…”

Recent Advances in the Asymmetric Catalytic Synthesis of Phosphonates with an α-Chiral Center

“…Template for SYNTHESIS Thieme enantioselectivities (Scheme 21a, 92%-99% yields , 84%->99% ee). 25 This protocol owned the advantages o f cheap transition metal nick el c atalytic system and great functional group toleranc e. The deuterium-labeling experiment results show ed that two hydrogen atom o f hydro genation products sho uld be from hydrogen, and a propos ed c atalytic mec hanism was illustrated in Scheme 21b for this asymmetric hydrogenation.…”

“…In 2023, we successfully realized that the nickel-catalyzed asymmetric hydrogenation of a variety of α-substituted α,β-unsaturated phosphine oxides, phosphonates, and phosphonic acids using commercially available ( S , S )-Ph-BPE as the ligand to give the corresponding chiral α-substituted phosphorus compounds in high yields and excellent enantioselectivities (Scheme 21a, 92–99 % yield, 84–>99% ee). 25 This protocol has the advantages of the cheap transition metal nickel catalytic system and great functional group tolerance. The results of deuterium-labeling experiments showed that two hydrogen atoms of the hydrogenation products are from hydrogen; a proposed catalytic mechanism is illustrated in Scheme 21b for this asymmetric hydrogenation.…”

Development of Construction of Chiral C—X Bonds through Nickel Catalyzed Asymmetric Hydrogenation★

“…该方法进一步应用于 (S)-诺氟西汀的不对称合成, 这是一种抗抑郁和焦虑的 有效选择性抑制剂(图 21). 图 24 镍催化 α-乙烯基膦化合物的不对称氢化反应衍生 Figure 24 Product derivatizations of nickel-catalyzed asymmetric hydrogenation of α-substituted vinylphosphine compounds 同 年 , 董 秀 琴 课 题 组 [41] 成 功 开 发 了 Ni(OAc) 2 /(S,S)-Ph-BPE 催化 α-取代 α,β-不饱和膦氧/膦酸 酯/膦酸化合物的不对称氢化反应, 以高收率和优异的 对映选择性获得了一系列手性 α-取代膦化合物(图 25). 2019 年 , 张 绪 穆 课 题 组 [42] 利 用 Ni(OAc) 2 /(S,S)-Ph-BPE 催化体系, 首次实现了镍催化 β-硼酸酯取代的 α,β-不饱和羧酸酯的不对称氢化反应, 以高收率和优异 的对映选择性合成了一系列手性 β-硼酸酯取代的羧酸 酯.…”