Nickel-Catalyzed Radical Heck-Type C(sp<sup>3</sup>)–C(sp<sup>2</sup>) Coupling Cascades Enabled by Bromoalkane-Directed 1,4-Aryl Shift: Access to Olefinated Arylalanines
Jian Liu, Yu Hong, Yin-Ling Liu, Jing-ying Tan, Haomiao Liu, Gang-Liang Dai, Shi‐Lu Chen, Ting Liu, Jin‐Heng Li, Shi Tang
Abstract
A bromoalkane-directed radical 1,4-aryl shift strategy for nickel-catalyzed reductive Heck-type C(sp3)–C(sp2) coupling cascades of α-amino-β-bromocarboxylic acid esters with α-trifluoromethyl alkenes for producing gem-difluorinated arylalanines is presented. The α-aminoalkyl radicals generated from neophyl-type aryl migration function as robust coupling partners to allow for further Giese-type addition with electron-deficient α-trifluoromethyl alkenes and vinyl sulfones, thereby realizing a new radical cascade for the simultaneous installation of an aromatic ring and olefin motif into amino acid backbones.
Topics & Concepts
ChemistryArylRadicalOlefin fiberCatalysisTrifluoromethylNickelMedicinal chemistryHeck reactionStereochemistryPalladiumCombinatorial chemistryOrganic chemistryAlkylRadical Photochemical ReactionsSulfur-Based Synthesis TechniquesCatalytic C–H Functionalization Methods