Control of Vicinal Stereocenters through Nickel‐Catalyzed Alkyl–Alkyl Cross‐Coupling

Abstract

Vicinal stereocenters are found in many natural and unnatural compounds. Although metal-catalyzed cross-coupling reactions of unactivated alkyl electrophiles are emerging as a powerful tool in organic synthesis, there have been virtually no reports of processes that generate, much less control, vicinal stereocenters. In this investigation, we establish that a chiral nickel catalyst can achieve doubly stereoconvergent alkyl–alkyl cross-couplings, specifically, reactions of a racemic pyrrolidine-derived nucleophile with cyclic alkyl halides (as mixtures of stereoisomers) to produce vicinal stereocenters with very good stereoselectivity.

Enantioconvergent Cross‐Couplings of Alkyl Electrophiles: The Catalytic Asymmetric Synthesis of Organosilanes

“…[15,16] indicating that C À Br bond cleavage is irreversible and that the chiral catalyst is processing both enantiomers of the electrophile in the stereoconvergent coupling of ar acemic electrophile (no dynamic kinetic resolution). [15,16] indicating that C À Br bond cleavage is irreversible and that the chiral catalyst is processing both enantiomers of the electrophile in the stereoconvergent coupling of ar acemic electrophile (no dynamic kinetic resolution).…”

“…[b] Yield of purified product (average of two experiments). [15,16] indicating that C À Br bond cleavage is irreversible and that the chiral catalyst is processing both enantiomers of the electrophile in the stereoconvergent coupling of ar acemic electrophile (no dynamic kinetic resolution). When an enantioconvergent cross-coupling of ar acemic electrophile is stopped at partial conversion, the unreacted electrophile is still racemic,i ndicating that the chiral catalyst is not discriminating between the enantiomeric electrophiles (no kinetic resolution).…”

Enantioconvergent Cross‐Couplings of Alkyl Electrophiles: The Catalytic Asymmetric Synthesis of Organosilanes

“…An enantioenriched α‐bromosilane does not racemize under the standard conditions [Eq. 2], indicating that C−Br bond cleavage is irreversible and that the chiral catalyst is processing both enantiomers of the electrophile in the stereoconvergent coupling of a racemic electrophile (no dynamic kinetic resolution). When an enantioconvergent cross‐coupling of a racemic electrophile is stopped at partial conversion, the unreacted electrophile is still racemic, indicating that the chiral catalyst is not discriminating between the enantiomeric electrophiles (no kinetic resolution) …”

Recentes Avanços Em Reações Orgânicas Catalisadas Por Níquel

“…A maioria desses processos exploram os estados de oxidação Ni(I)/Ni(III), que são raros quando comparamos ao Pd. Outros processos envolvendo Ni vêm sendo desenvolvidos, tais como acoplamento descarboxilativo 43 e acoplamento cruzado assimétrico envolvendo eletrófilos alquila 44,45 .…”