Copper Catalyzed Enantioconvergent Nucleophilic Substitutions

As a versatile earth-abundant transition metal,Cu has long been widely applied in the C—C and C—X bond forming reactions.As for now,low-valent Cu(Ⅰ)is known to reduce the redox active electrophiles via an SET pathway to give the corresponding radical and Cu(Ⅱ)species.The resulting Cu(Ⅱ)species can interact with the radical via the out-sphere pathway,affording the coupling product.Alternatively,Cu(Ⅱ)can trap the radical through the inner-sphere process to generate Cu(Ⅲ)species and then realize challenging bond formations due to the facile reductive elimination of Cu(Ⅲ)intermediate.Although copper catalysis has been widely applied in arylations of various nucleophiles,copper-catalyzed enantioconvergent nucleophilic substitutions of racemic alkyl electrophiles have been less explored,likely due to the difficulties in overcoming the reduction potential of alkyl electrophiles,elimination of side reactions,and enantiomeric control.In order to overcome the high reduction potential of alkyl electrophiles,the photo-induced strategy has been developed under mild conditions.An alternative strategy with new anionic tridentate ligands has also been reported in this regard.This review summarizes recent developments in copper-catalyzed enantioconvergent nucleophilic substitutions of alkyl electrophiles by various nucleophiles to realize C—N,C—C,C—B,C—P and C—O bond formations and their brief mechanistic studies.

Ni-Catalyzed Enantioconvergent Coupling of Epoxides with Alkenylboronic Acids:Construction of Oxindoles Bearing Quaternary Carbons

We have developed a nickel-nickel/bisphosphinecatalyzed stereoconvergent cross-coupling reaction of epoxides with alkenylboronic acids.Racemic spiroepoxyoxindoles were converted to chiral homoallylic alcohols bearing quaternary carbon stereogenic centers via a stereoablative enantioconvergent transformation.The subsequently fabricated oxindoles-carrying quaternary carbon products were obtained in good yields and enantioselectivity.A wide range of substrates and alkenylboronic acids was tolerated under the catalytic system.This reaction provided a rare example of a nickelcatalyzed enantioselective cross-coupling reaction of tertiary alkyl electrophiles and an enantioconvergent transformation of racemic epoxides,beneficial as a low-cost,sustainable,and efficient catalyst in the preparation of chiral oxindole-containing natural and pharmaceutical compounds.

Enantioconvergent photoredox radical-radical coupling catalyzed by a chiral-at-rhodium complex

Racemicα-chloro imidazol-2-yl-ketones undergo an enantioconvergent photoactivated C–C bond formation with N-aryl glycines catalyzed by a single bis-cyclometalated chiral-at-rhodium catalyst in yields of up to 80%and up to 98%enantiomeric excess(ee).Control experiments support a mechanism which is initiated by a single electron transfer from N-aryl glycinate to the photochemically excited rhodium-boundα-chloro imidazol-2-yl-ketone,followed by chloride fragmentation of theα-chloroketone,decarboxylation of the glycinate,and a subsequent highly stereocontrolled radical-radical coupling.This work showcases the ability of the chiral rhodium catalyst to serve a dual function as chiral Lewis acid and at the same time as the photoredox active species upon substrate binding.