Asymmetric Three-Component Radical Cascade Reactions Enabled by Synergistic Photoredox/Brønsted Acid Catalysis: Access to α-Amino Acid Derivatives
Chao Che, Yi‐Nan Lu, Ting Fang, Guangjin Zhen, Xiaotian Qi, Chun‐Jiang Wang
Abstract
High Resolution Image Download MS PowerPoint Slide Multicomponent reactions (MCRs), highly sought-after methods to produce atom-, step-, and energy-economic organic syntheses, have been developed extensively. However, catalytic asymmetric MCRs, especially those involving radical species, remain largely unexplored owing to the difficulty in stereoselectively regulating the extraordinarily high reactivity of open-shell radical species. Herein, we report a conceptually novel catalytic asymmetric three-component radical cascade reaction of readily accessible glycine esters, α-bromo carbonyl compounds and 2-vinylcyclopropyl ketones via synergistic photoredox/Brønsted acid catalysis, in which three sequential C–C (σ/π/σ) bond-forming events occurred through a radical addition/ring-opening/radical–radical coupling protocol, affording an array of valuable enantioenriched unnatural α-amino acid derivatives bearing two contiguous stereogenic centers and an alkene moiety in moderate to good yield with high diastereoselectivity, excellent enantioselectivity and good E -dominated geometry under mild reaction conditions. The radical relay cascade process, especially a unique proton-coupled electron transfer (PCET)-promoted radical–radical coupling, is supported by mechanistic investigations and quantum mechanics calculations and should garner broad interest and further inspire the development of asymmetric multicomponent radical reactions.