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Borrowing Carbonate-Enabled Allylic Amination Reactions under Additive- and Reductant-Free Nickel Catalysis Employing Allylic Alcohols

Gargi Nikhil Vaidya, Mithilesh Nagpure, Dinesh Kumar

2021ACS Sustainable Chemistry & Engineering18 citationsDOI

Abstract

A “borrowing carbonate”-enabled allylic cross-amination reactions employing allylic alcohol were discovered via merging acyl/allyl C–O bonds activation under nickel catalysis. The key component of this protocol is the ability of nickel [Ni(II)-Ni(0)] to execute a relay process via the nucleophilic trapping of the generated acyl Ni complex, resulting from the acyl C–O bond cleavage of dialkyl carbonates, followed by selective allylic C–O bond activations (allylic C–O vs alkyl C–O vs acyl C–O) to yield π-allylNi-complexes. The finding truly represents Ni-catalyzed green allylic amination reactions under additive(s)-free conditions with excellent chemo- (N vs O), regio- (linear vs branched), and stereoselectivity (E vs Z) with a wide range of fundamentally challenging N-heterocycles and allylic alcohols. The reaction is scalable, does not require harmful reaction media and a globe box, and is successfully applied to the scale-up synthesis of pharmaceuticals (cinnarizine, flunarizine, and naftifine) with promising yields.

Topics & Concepts

Allylic rearrangementAminationChemistryCatalysisNucleophileMedicinal chemistryOrganic chemistryCombinatorial chemistryCatalytic C–H Functionalization MethodsAsymmetric Hydrogenation and CatalysisCatalytic Cross-Coupling Reactions
Borrowing Carbonate-Enabled Allylic Amination Reactions under Additive- and Reductant-Free Nickel Catalysis Employing Allylic Alcohols | Litcius