Litcius/Paper detail

Chiral Allylic Amine Synthesis Enabled by the Enantioselective Cp<sup>X</sup>Rh(III)-Catalyzed Carboaminations of 1,3-Dienes

Liexin Wu, Huiying Xu, Hui Gao, Liping Li, Weijie Chen, Zhi Zhou, Wei Yi

2021ACS Catalysis42 citationsDOI

Abstract

Considering the importance of the chiral allylic amine structural motif and the rarity of synthetic methods toward their construction, herein, we report a CpXRh(III)-catalyzed enantioselective intermolecular carboamination of 1,3-dienes via N-phenoxy amides-derived intermolecular aryl C–H activation and intramolecular amide transfer. The methodology enables the direct synthesis of a variety of chiral allylic amines with the embedment of phenol functionalities and proceeds under mild conditions with sequential formation of a completely regioselective C–C bond and a highly enantioselective C–N bond. Integrated experimental and computational mechanistic studies reveal an unusual Rh(III)–Rh(I)–Rh(III) catalytic pathway, in which an alkene insertion/π-allylation/intramolecular nucleophilic substitution cascade was involved for this transformation. Besides, synthetic application in the derivation of natural products and the late-stage assembly of bioactive complexes has also been demonstrated, which further strengthens the synthetic utility of this approach.

Topics & Concepts

Enantioselective synthesisAllylic rearrangementChemistryIntramolecular forceRegioselectivityAlkeneCatalysisAminationNucleophileCombinatorial chemistryStereochemistryArylIntermolecular forceMedicinal chemistryOrganic chemistryMoleculeAlkylCatalytic C–H Functionalization MethodsAsymmetric Synthesis and CatalysisSynthesis and Catalytic Reactions