Enantioselective C(sp³)–C(sp³) Reductive Cross-Electrophile Coupling of Unactivated Alkyl Halides with α-Chloroboronates via Dual Nickel/Photoredox Catalysis

Abstract

Substantial advances in enantioconvergent C(sp3)–C(sp3) bond formations have been made with nickel-catalyzed cross-coupling of racemic alkyl electrophiles with organometallic reagents or nickel-hydride-catalyzed hydrocarbonation of alkenes. Herein, we report an unprecedented enantioselective C(sp3)–C(sp3) reductive cross-coupling by the direct utilization of two different alkyl halides with dual nickel/photoredox catalysis system. This highly selective coupling of racemic α-chloroboronates and unactivated alkyl iodides furnishes chiral secondary alkyl boronic esters, which serve as useful and important intermediates in the realm of organic synthesis and enable a desirable protocol to fast construction of enantioenriched complex molecules.

Selectively Tunable Synthesis of α-Trifluoromethyl Ketones

“…Very recently, a cross-coupling of α-trifluoromethyl alkyl bromides and aryl halides to deliver benzylic trifluoromethylation products under dual nickel/photoredox catalysis system has been developed in our group. , Considering that tetrabutylammonium decatungstate (TBADT) can serve as an efficient hydrogen-atom-transfer (HAT) photocatalyst for the acyl C–H activation of aldehydes, we envisioned a coupling of α-trifluoromethyl alkyl bromides and aldehydes could provide a facile and modular route to obtain α-CF 3 ketones (Scheme bottom). Importantly, by the utilization of various substrates, the CF 3 group can be selectively installed into any one side of the carbonyl which can well circumvent the aforementioned problems in the enolate process.…”

Ni-Electrocatalytic Enantioselective Doubly Decarboxylative C(sp3)–C(sp3) Cross Coupling

“…Indeed, numerous studies built off of those seminal findings to combine electrophilic ester and amide derivatives with olefins under Ni-catalysis (Figure A). − In 2022, the Fu group further demonstrated that in situ generated Reformansky-type reagents could be coupled to alkyl halides in an enantioselective fashion (Figure B) . Recent findings from the Xu group have subsequently demonstrated that two electrophiles such as α-halo boronic esters and alkyl halides could also be coupled with high enantiocontrol under photoreductive conditions (Figure C) . Meanwhile, doubly decarboxylative cross coupling (dDCC) has emerged as a powerful method to construct Csp 3 –Csp 3 bonds under electrochemical conditions (with and without Ni, Figure D). − In this Communication, the first examples of enantio- and diasteroselective dDCC between redox-active esters (RAEs) derived from readily available alkyl carboxylic acids and malonate derivatives are disclosed .…”

“…8 Recent findings from the Xu group have subsequently demonstrated that two electrophiles such as α-halo boronic esters and alkyl halides could also be coupled with high enantiocontrol under photoreductive conditions (Figure 1C). 9 Meanwhile, doubly decarboxylative cross coupling (dDCC) has emerged as a powerful method to construct Csp 3 −Csp 3 bonds under electrochemical conditions (with and without Ni, Figure 1D). 10−12 In this Communication, the first examples of enantio-and diasteroselective dDCC between redox-active esters (RAEs) derived from readily available alkyl carboxylic acids and malonate derivatives are disclosed.…”

A Pd-catalyzed organometallic-free homologation of arylboronic acids enabled by chemoselective transmetalation

“…Halomethylorganoboron reagents have been shown to display several different reactivity profiles, including metalation, boronate formation, and the formation of a-boryl radicals; however, examples of oxidative addition to this reagent class remain rare and are principally achieved using Ni catalysis. For example, Fu demonstrated stereoconvergent crosscoupling of racemic a-chloroboronic acid esters with organozinc reagents, 40,41 while Martin first showed crosselectrophile coupling [42][43][44] and alkene difunctionalization using a-bromoboronic acid esters. 45 Within Pd catalysis, Gevorgyan has developed Heck reactions based on a single-electron transfer (SET) manifold.…”

“…Several heterocycles were well tolerated including thiophenes (39)(40)(41), pyridine (42), furans (43,44), and isoxazole (45). Some limitations of the boronic acid scope included specific functional groups (46,47), heterocycles (48, 49), styrene boronic acid (50), and alkylboronic acids (51).…”