Nickel-catalyzed asymmetric reductive arylation of α-chlorosulfones with aryl halides.

Deli Sun,Chuanhu Lei,Hegui Gong,Guobin Ma,Xinluo Zhao

doi:10.1039/d1sc00283j

Abstract

We report an asymmetric Ni-catalyzed reductive cross-coupling of aryl/heteroaryl halides with racemic α-chlorosulfones to afford enantioenriched sulfones. The reaction tolerates a variety of functional groups under mild reaction conditions, which complements the current methods. The utility of this work was demonstrated by facile late-stage functionalization of commercial drugs.

Highlights

We report an asymmetric Ni-catalyzed reductive cross-coupling of aryl/heteroaryl halides with racemic achlorosulfones to afford enantioenriched sulfones
The reaction tolerates a variety of functional groups under mild reaction conditions, which complements the current methods
Our investigations began with the coupling between 1 and 2 using chiral bis(oxazoline) ligands (Table 1)

Summary

Introduction

Sulfones are important functional units in synthetic chemistry1 and unique compounds that have been widely studied in medicinal chemistry.2 Among them, a number of alkyl sulfones are FDA-approved drugs (e.g., bicalutamide for prostate cancer and apremilast for psoriatic arthritis).3 Many efforts based upon transition-metal catalyzed coupling reactions have been devoted to the functionalization of the a-positions of alkylsulfones.4–6 asymmetric methods are largely con ned to Tsuji–Trost allylation and Michael addition reactions by virtue of formation of relatively stable a-sulfonyl carbanions.6 Fu and co-workers have reported the rst enantioselective Negishi coupling of a-bromosulfonamides and -sulfones with organozinc and organozirconium reagents to furnish secondary benzylic and allylic sulfonamides and sulfones in good yields and high levels of enantioselectivities.7 Asymmetric alkylation of a-bromosulfonamides with alkenes was later found to be effective under Ni–H–alkene insertion/ alkylation conditions which afforded enantioenriched a-alkyl sulfones and sulfonamides.8 In both cases, the involvement of a-sulfonyl carbon radicals is thought to be key. We report an asymmetric Ni-catalyzed reductive cross-coupling of aryl/heteroaryl halides with racemic achlorosulfones to afford enantioenriched sulfones. Asymmetric introduction of heteroaromatics to the a-carbon of sulfones remains elusive.8,9 Second, the substrate scope may be limited with the current methods due to the use of organometallic nucleophiles and terminal alkenes.7,8 We envision that a cross-electrophile coupling strategy that utilizes readily accessible aryl

Results

Conclusion