Shenzhen Key Laboratory of Cross-Coupling Reactions, Southern University of Science and Technology, Shenzhen, 518055, China.
Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen, 518055, China.
Angew Chem Int Ed Engl. 2023 Jul 3;62(27):e202302983. doi: 10.1002/anie.202302983. Epub 2023 May 22.
Transition-metal catalyzed enantioconvergent cross-coupling of tertiary alkyl halides with ammonia offers a rapid avenue to chiral unnatural α,α-disubstituted amino acids. However, the construction of chiral C-N bonds between tertiary-carbon electrophiles and nitrogen nucleophiles presented a great challenge owing to steric congestion. We report a copper-catalyzed enantioconvergent radical C-N cross-coupling of alkyl halides with sulfoximines (as ammonia surrogates) under mild conditions by employing a chiral anionic N,N,N-ligand with a long spreading side arm. An array of α,α-disubstituted amino acid derivatives were obtained with good efficiency and enantioselectivity. The synthetic utility of the strategy has been showcased by the elaboration of the coupling products into different chiral α-fully substituted amine building blocks.
过渡金属催化的三级卤代烃与氨的对映选择性交叉偶联为手性非天然α，α-二取代氨基酸提供了快速途径。然而，由于空间位阻，三级碳亲电试剂与氮亲核试剂之间手性 C-N 键的构建极具挑战性。我们报告了一种铜催化的在温和条件下，通过使用带有长伸展侧臂的手性阴离子 N，N，N-配体，实现了烷基卤化物与亚砜亚胺（作为氨的替代物）的对映选择性自由基 C-N 交叉偶联。通过该策略，一系列 α，α-二取代氨基酸衍生物以良好的效率和对映选择性得到了合成。该策略的合成实用性已通过将偶联产物转化为不同的手性 α-完全取代的胺构建块得到了展示。
