Nakamura Shogo, Nishino Soshi, Hirano Koji
Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871, Japan.
Innovative Catalysis Science Division, Institute for Open and Transdisciplinary Research Initiatives (ICS-OTRI), Osaka University, Suita, Osaka 565-0871, Japan.
J Org Chem. 2023 Jan 20;88(2):1270-1281. doi: 10.1021/acs.joc.2c02632. Epub 2023 Jan 11.
A copper-catalyzed regioselective hydroamination of α,β-unsaturated phosphonates has been developed to form corresponding α-aminophosphonates of interest in medicinal chemistry. The introduction of an umpolung, electrophilic amination strategy with the hydroxylamine derivative is the key to achieving the α-amination regioselectivity, which is otherwise difficult under the conventional nucleophilic hydroamination conditions with the parent amine. Asymmetric synthesis with a chiral bisphosphine ligand and application to a related silylamination reaction are also described.
已开发出一种铜催化的α,β-不饱和膦酸酯区域选择性氢胺化反应，以形成药物化学中感兴趣的相应α-氨基膦酸酯。引入一种极性反转的亲电胺化策略，使用羟胺衍生物，是实现α-胺化区域选择性的关键，否则在使用母体胺的常规亲核氢胺化条件下很难实现。还描述了使用手性双膦配体的不对称合成及其在相关硅胺化反应中的应用。
