偶联反应小结

偶联反应小结经典反应式Cross-CouplingReactionsCatalystMRR'XKumada-Corriu(1972)NiorPdMgAryl,alkyl,vinylAryl,alkyl,vinylCl,Br,I,OTsSonogashira(1975)Pd/CuICuAryl,alkylAryl,alkyl,vinylBr,INegishi(1977)NiorPdZnAryl,allyl,benzyl,propargylAryl,alkyl,vinyl,alkynyl,benzyl,allylCl,Br,I,OTsStille(1978)PdSnAryl,vinyl,benzyl,alkynylAryl,alkyl,vinyl,benzyl,allyl,acylCl,Br,I,OTsSuzuki(1979)PdBAryl,alkylAryl,alkyl,alkynylCl,Br,I,OTsHiyama(1988)NiorPdSiArylAryl,alkyl,vinylBr,I,OTsKumada,Suzuki,Stille,Negishi,Hiyamacoupling(C-CFormation:C-X+C-M)Buchwald-Hartwigcoupling(C-N,C-O,C-SFormation:C-X+Nu(N,O,S)-H)a-ArylationofKetone(C-CFormation:C-X+C-H)Heck,Sonogashiracoupling(AlkeneandalkyneFormation:C-X+C-H)GeneralMechanismKumada,Kumada-Corriu

Coupling1960年Chatt和Shaw:

1970年Uchino等:

Sp3C-Xsubstrate?大家有疑问的，可以询问和交流可以互相讨论下，但要小声点配体得影响

格氏试剂上烷基部分得异构化

Fe-catalystLowinitialtemperature(-20°C)isbeneficialMolander,G、A、et、al、TetrahedronLett、

1983,24,5449、NewdevelopmentofthecatalystArylchlorides,triflatesandtosylatesarebettersubstratesthanarylbromidesandiodidesEntryXYield(GC,%)ab1I27462Br38503Cl>95-4OTf>95-5OTs>95-Fürstner,A、et、al、Angew、Chem、Int、Ed、Engl、

2002,41,609、β-Hydrideeliminationandhomocouplingarethemajorsetbackwiththecross-couplingof1oand2oalkylsubstrateswitharylGrignardreagentsEntrySolventProductYield(%)CDEF*1THF/NMP252524262THF272720253Et2O601912124Et2O(reflux)691899Hayashi,T、et、al、Org、Lett、

2004,6,1297、*Amountafter0、05mmol(equivalenttocatalyst)subtracted、

AlkylDerivativesasSubstrateAlkylDerivativesasSubstrateTMEDAplaysacrucialroletoreduceβ-hydrideeliminationEntryaAdditiveProductYield(GC,%)CDEAF1None5790462Et3N37801153N-Methylmorpholine8720454DABCO20207535NMP153Trace7946TMEDA71193Trace10Nakamura,E、et、al、J、Am、Chem、Soc、

2004,126,3686、aPhMgBr(1、2equiv),additive(1、2equiv),30min、Fürstner,A、et、al、Angew、Chem、Int、Ed、

2003,42,308、Fürstner,A、et、al、J、Org、Chem、

2004,69,3950、SynthesisofR-(+)-MuscopyridineandimmunosuppressiveagentFTY720Fürstner,A、et、al、Angew、Chem、Int、Ed、

2003,42,5358、SynthesisofLatrunculinBIndustrialexamplesHokkoChemicalIndustry,JapanScale:20t/ySolvent:FromEthertoTHF,withTolueneasco-solvent、Pd(PPh3)4TON74,000910,000环钯催化剂PtBu328,000,000ArClsubstrateWatersoluble反应底物有机硼酸(酯)ArBr经格氏反应,或者nBuLi,与B(OR)3反应得到硼氢化反应Losartan,Merck(1994),抗高血压药物JOC,1994,59,6391PharmaciaCo、andDow抗真菌剂fungizideBoscalid,BASF,1000t/yCancercellgrowthinhibitor,NovartisTreatmentforHIVStille偶联,Still