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Ni-Catalyzed Diastereoconvergent Intramolecular Alkene–Aldehyde Reductive Coupling: A Route to <i>syn</i>-Chromanols

Sudipta Kumar Ghosh, Arnab Rooj, Rajesh Chakrabortty, Venkataraman Ganesh

2024Organic Letters9 citationsDOI

Abstract

We demonstrate for the first time a nickel-catalyzed diastereoconvergent reductive coupling of a heteroatom-attached allyl moiety with aldehydes, viz., O -allyl, O -cinnamyl salicylaldehydes, and others, to afford syn -chromanols exclusively. The reaction proceeds through a [2 + 2 + 1] oxidative cycloaddition involving the active catalyst. This method is applicable to both terminal and internal olefin substrates. The formal syntheses of CP-199.330, CP-199.331, and CP-85.958 have been demonstrated. Control experiments, mass spectrometric analysis, and DFT studies supported the plausible mechanism and the origin of exclusive syn -selectivity.

Topics & Concepts

ChemistryIntramolecular forceAlkeneAldehydeCatalysisCoupling (piping)Combinatorial chemistryMedicinal chemistryStereochemistryOrganic chemistryMechanical engineeringEngineeringCatalytic C–H Functionalization MethodsAsymmetric Hydrogenation and CatalysisCatalytic Cross-Coupling Reactions
Ni-Catalyzed Diastereoconvergent Intramolecular Alkene–Aldehyde Reductive Coupling: A Route to <i>syn</i>-Chromanols | Litcius