Catalytic enantioconvergent coupling of secondary and tertiary electrophiles with olefins

Abstract

Carbon-carbon bonds, including those between sp 3 -hybridized carbons (alkyl-alkyl bonds), typically comprise much of the framework of organic molecules. In the case of sp 3 -hybridized carbons, the carbon can be stereogenic, and the particular stereochemistry can have implications for structure and/or function 1 , 2 , 3 . As a consequence, the development of methods that simultaneously construct alkyl-alkyl bonds and control stereochemistry is a highly important, as well as a challenging, objective. Herein, a new strategy for enantioselective alkyl-alkyl bond formation is described, wherein a racemic alkyl electrophile is coupled with an olefin in the presence of a hydrosilane, through the action of a chiral nickel catalyst. Families of racemic alkyl halides, including tertiary substrates, that have not previously proved to be suitable for enantioconvergent couplings with alkylmetal nucleophiles are shown to cross-couple with olefins with good enantioselectivity and yield under very mild conditions. Given the ready availability of olefins, this new approach opens the door to the development of ever more general and powerful methods for enantioconvergent alkyl-alkyl coupling.

Stereoinvertive C–C Bond Formation at the Boron‐Bound Stereogenic Centers through Copper‐Bipyridine‐Catalyzed Intramolecular Coupling of α‐Aminobenzylboronic Esters

“…a-Aminobenzylboronates bearing fully substituted boron-bound stereogenic centers also gave the 3,3-disubstituted isoindolinones with stereospecific stereochemical inversion in the presence of simple 2,2'-bipyridine as a ligand.Cross-coupling reactions to form stereogenic sp 3 -carbon centers [1] are recognized as a highly attractive transformations in asymmetric synthesis. Most typically, enantioenriched or racemic chiral secondary alkyl electrophiles are used in the coupling with achiral organometallic reactants, leading to stereospecific [2] or enantioconvergent [3] cross-coupling. In addition to such coupling using chiral electrophiles, stereospecific cross-couplings using configurationally stable chiral organometallic compounds [4][5][6][7] have gained increasing attention.…”

Nickel‐Catalyzed Regioselective Hydroalkylation and Hydroarylation of Alkenyl Boronic Esters

“…The details of the mechanism of this hydrocarbonation reaction will be investigated in a future study, so only a preliminary hypothesis is provided here. The reaction proceeds through the formation of a NiH species from the Ni catalyst and silane, followed by insertion of the NiH species into the alkene . The insertion is selective and occurs at the carbon atom α to the boryl group probably because of electronic stabilization.…”

Nickel‐Catalyzed 1,1‐Alkylboration of Electronically Unbiased Terminal Alkenes

“…β‐H elimination then delivers the nickel complex IV , and subsequent rapid migratory insertion affords a new stable alkylNi(II) intermediate ( V ), which reacts with an activated alkyl halide ( 2 ), giving rise to the 1,1‐difunctionalized product ( 4 ). The reaction of intermediate V with the alkyl halides likely involves a radical‐chain process, but another possibility involving dual nickel transmetalation cannot be ruled out at this stage . Further mechanistic investigations are currently underway in our laboratory.…”