McMurry-coupling

McMurrycouplingContentIntroduction1Intermolecularreactions2Intramolecularreactions3Summary4McMurrycouplingTheMcMurryreactionisanorganicreactioninwhichtwoketoneoraldehydegroupsarecoupledtoanalkeneusingtitaniumchloridecompoundsuchastitanium(III)chlorideandareducingagent.MechanismFeaturesThelow-valenttitanium:TiCl3with(Zn-Cu);Atlowtemperature:thepinacolintermediatemaybeisolated;Athightemperaturethealkenesareformeddirectly;Stericallyhinderedand/orstrainedolefins(tetrasubstitutedalkenes);Macrocyclization(highdilution);Intramolecularreactionsarethefastestfortheformationoffive-andsix-memberedringsandtheformationofeight-orhigher-memberedringsisconsiderablyslower;Aldehydesreactmuchfasterthanketones:chemoselectivity;Poorstereoselectivity:preferencefor(E)-alkenes;Homocouplingandmixedcoupling.Well-controlledintermolecularMcmurrycoupling——synthesisofamolecularmotormolecularmotor:Light/heatdrivenconfigurationtransformation合成的难点：•双键位阻大，较难形成；•避免手性碳的消旋化；•避免脱卤反应；钛试剂的选择：TiCl4orTlCl3路易斯酸性过强会导致α位的手性碳消旋化还原剂的选择：还原剂原料ee值/%产率/%E/Z产物ee值/%Zn897550/5093LiAlH4893840/6098•LiAlH4做还原剂时，有明显的脱溴反应（可能和TiH2产生有关），且有较多的单分子还原产物。反应机理：Thomas,M.N.;Ben,L.;et.al.,Org.Lett.2014,16,4220.McMurrycouplingofarylaldehydesandiminopinacolcouplingmediatedbyTi(O-i-Pr)4/Me3SiCl/MgreagentOkamoto,S.;He,J.;et.al.,TetrahedronLett.2010,51,387-390.J.E.McMurry,K.L.Kees,J.Org.Chem.1977,42,2655–2656.H.Hopf,C.Mlynek,J.Org.Chem.1990,55,1361–1363.Intramolecularreactions非天然产物合成Y.Li,W.Li,Y.Li,Synth.Commun.1994,24,721–726.烟草四烯CJ.E.McMurry,D.D.Miller,TetrahedronLett.1983,1885–1888.异石竹烯ApplicationofMcMurryReactioninSynthesisofNaturalProductsEphritikhine,M.,Villiers,C.ModernCarbonylOlefination2004,223-285.Eguchi,T.,Ibaragi,K.,Kakinuma,K.J.Org.Chem.1998,63,2689-2698.Mikami,K.,Takahashi,K.,Nakai,T.J.Am.Chem.Soc.1990,112,4035-4037.Liu,Z.,Zhang,T.,Li,Y.TetrahedronLett.2001,42,275-277.SummaryMcMurry反应是指醛、酮在低价钛的作用下发生还原二聚形成烯烃的反应；低价钛试剂一般由TiCl3经LiAlH4或碱金属或Mg或Zn(Cu)还原形成；醛、酮的偶联反应可以分子间或分子内方式形成，分别用于链状或环烯烃的合成；从小环烯烃到大环烯烃，包括索烃和72元大环四醚脂类烯烃均可形成；酮-酮，酮-酯，酮-酰胺羰基间的交叉偶联也可进行。ThanksForYourAttentionTheEnd