康 · 学术 | Reaction of the Day No. 1321

ReductiveAlkyl–alkylCouplingfromIsolableNickel–alkylComplexes

SamirAlZubaydi[a],ShivamWaske[a]†,VolkanAkyildiz[a,b]†,[a],MayukhMajumder[a],[a],DipannitaKalyani[c]*[a]*

[a]DepartmentofChemistryandBiochemistry,TheOhioStateUniversity,Columbus,OH,USA.

[b]DepartmentofChemistry,FacultyofScience,AtatürkUniversity,Erzurum,Turkey.

[c]DiscoveryChemistry,,Rahway,NJ,USA.

†Theseauthorscontributedequallytothiswork.

—Nature,2024,DOI:10.1038/s47-9

RecommedbyRuiJin_MC5

KEYWORDS:Reductivealkyl–alkylcoupling(反应类型),electrochemistry(反应类型),C(sp3)–C(sp3)(成键类型),Ni(alkyl)complexes(催化剂/试剂),alkylhalides(原料),redox-activeesters(原料),pyridiniumsalts(原料),alkane(产物)

ABSTRACT:Theselectivecross-couplingoftwoalkylelectrophileabletointerchangeablyvaryingelectrophilicsubstratesthataresourcedfromcommonalkylbuildingblocks,suchasamines,edand,ultimately,natorialapproachtoalkyl–(alkyl)complexesthatcanbeformeddirectlybyoxidativeadditionofalkylhalides,uplewithasecondalkylelectrophile,ficationofaminoacids,naturalproducts,pharmaceuticalsanddrug-likebuildingblocksbyvariouscombinationsofdehalogenative,,thisworkprovidesinsightsintotheorganometallicchemistryofsyntheticallyrelevantNi(alkyl)complexesthroughcrystallographicanalysis,stereochemicalprobesandspectroscopicstudies.

(A)Selectivityinalkylcross-couplingreactions.(B)Stoichiometricstrategyforcross-couplingofalkylelectrophiles

(C)ComparisonofsyntheticroutesforNi(alkyl)andsubsequentreactivity

Combinatorialcross-couplingreactionsofalkylRAEs,bromidesandpyridiniumsalts

Yieldshighlightedingreyboxesarefromelectrochemicalreactions,allotheZnrsareperformedwith.

ParallelelectrolysisreactionsperformedinHTe−Chem

Thepurplecircleshighlightthecarbonatomsotsintroducedinthesecondstep.

Substratescope:applicationtocomplexmolecules

SummaryandComments

Collectively,thesefindingsunderscoretheimportanceofdesigningalkylcomplexeswithhighpersistencetoundergoarelative,insightsintothemechanismsofOAandREfacilitatedthereliablesynthesisofpersistentNi(alkyl)complexesandimprovedthesyntheticutilityoftheorg,manyoftheexamplesinthisworkrepresentpreviouslyunkgcouplingreactionsaswellasforfundamentalstudiesintotheorganometallicchemistryofNi–alkylcomplexes.

DipannitaKalyani和课题组以一种可分离的烷基镍络合物为中间体，实现了还原烷基-烷基偶联反应。关键中间体烷基镍络合物可以通过烷基卤化物氧化加成、氧化还原活性酯或吡啶盐直接形成，可以分离或者直接与第二个烷基亲电试剂偶联。该反应可以在氨基酸、天然产物和药物分子结构单元之间通过脱卤、脱羧或脱酰胺偶联实现高效多样化组合，扩展了传统烷基-烷基反应的底物适用范围。