[理学]有机合成化学 5.ppt

《[理学]有机合成化学 5.ppt》由会员分享，可在线阅读，更多相关《[理学]有机合成化学 5.ppt（69页珍藏版）》请在taowenge.com淘文阁网|工程机械CAD图纸|机械工程制图|CAD装配图下载|SolidWorks_CaTia_CAD_UG_PROE_设计图分享下载上搜索。

1、理学理学有机合成化学有机合成化学 5Modern Organic Synthesis22010 Nobel prize 瑞典皇家科学院说，这三名科学家因在有机合成领域中钯催化交叉偶瑞典皇家科学院说，这三名科学家因在有机合成领域中钯催化交叉偶联反应方面的卓越研究获奖。这一成果广泛应用于制药、电子工业和先联反应方面的卓越研究获奖。这一成果广泛应用于制药、电子工业和先进材料等领域，可以使人类造出复杂的有机分子。进材料等领域，可以使人类造出复杂的有机分子。赫克赫克,79,79岁，美国特拉华大学名誉教授；根岸荣一岁，美国特拉华大学名誉教授；根岸荣一,75,75岁岁, ,美国普渡大美国普渡大学化学教授；铃

2、木彰学化学教授；铃木彰,80,80岁岁, ,日本札幌北海道大学教授。日本札幌北海道大学教授。Modern Organic Synthesis3Glaser (Hay) CouplingModern Organic Synthesis4Suzuki CouplingPd or NiBaseR1X2RB(OH)2+1RR2Modern Organic Synthesis5R1HXR2+R1R2Pd-Complex, CuIAmineSonogashira ReactionModern Organic Synthesis6Modern Organic Synthesis7Amination Reac

3、tionModern Organic Synthesis8Modern Organic Synthesis9Stille reactionModern Organic Synthesis10Modern Organic Synthesis11The Kumada Coupling was the first Pd or Ni-catalyzed cross coupling reaction, developed in 1972. Kumada reactionModern Organic Synthesis12Modern Organic Synthesis13Negishi reactio

4、nModern Organic Synthesis14Modern Organic Synthesis15Modern Organic Synthesis16Fukuyama Coupling Modern Organic Synthesis17Modern Organic Synthesis18Heck reactionModern Organic Synthesis19Modern Organic Synthesis20过渡金属催化的烯烃、炔烃过渡金属催化的烯烃、炔烃复分解反应复分解反应Metathesis年度诺贝尔化学奖年度诺贝尔化学奖for the development of the

5、 metathesis method in organic synthesis.Modern Organic Synthesis21Yves Chauvin，伊夫肖万 lInstitut franais du ptrole, Rueil-Malmaison, France.Robert H. Grubbs,罗伯特格拉布 California Institute of TechnologyRichard R. Schrock,理查德施罗克 Massachusetts Institute of TechnologyModern Organic Synthesis22Metathesis a cha

6、nge-your-partners dance Metathesis can be viewed as a dance of two molecules, with a catalyst pair (left) that includes a metal (black) joining hands with an alkene (yellow/red) pair. The pair then join in a circle (center), and then go off with different partners (right). Modern Organic Synthesis23

7、 This years Nobel Prize Laureates in chemistry have made metathesis into one of organic chemistrys most impor-tant reactions. Fantastic opportunities have been created for producing many new molecules - pharmaceuticals, for example. Imagination will soon be the only limit to what molecules can be bu

8、ilt!Modern Organic Synthesis24烯烃复分解反应烯烃复分解反应R1R2cata.R1R1R2R2Modern Organic Synthesis25MR2R1R1MR2R1R1MR1R1R2Modern Organic Synthesis26MH3CMH3CMCH3MCH3MCH3CH3CH3H3CCH3MH3Ccata.+H3CCH3Modern Organic Synthesis27MH3CMH3CMMCH3CH3CH3H3CCH3Modern Organic Synthesis28Grubbs 催化剂的制备催化剂的制备Modern Organic Synthes

9、is29Modern Organic Synthesis30Modern Organic Synthesis31R1R2cata.R1R1R2R2炔烃复分解反应炔烃复分解反应Modern Organic Synthesis32Modern Organic Synthesis33Modern Organic Synthesis34Modern Organic Synthesis35过渡金属催化的偶联反应反应过渡金属催化的偶联反应反应最新研究进展最新研究进展General IntroductionRX+RMCatalystR RRX = RI, RBr, RCl, R-OR, R-NR2; RM

10、= R-Metal, R-HCross-Coupling ReactionHeck Coupling:R1X+Ligand, Base SolventHR1R2R3Pd(0) (catalytic)R1R1R2R3Heck, R. F. J. Am. Chem. Soc. 1968, 90, 5518Modern Organic Synthesis36Kumada Coupling:RX+RMgXNiCl2L2 (cat)Pd(0) (catalytic)RRSolvent/ LigandTamao, K.; Kiso, Y.; Sumitani, K.; Kumada, M. J. Am.

11、Chem. Soc. 1972, 94, 9268Tamao, K.; Sumitani, K.; Kumada, M. J. Am. Chem. Soc. 1972, 94, 4374Suzuki Coupling:RX+ RB(R)3RRLigand, Base SolventPd(0) (catalytic)Miyaura, N.; Suzuki, A. J. Chem. Soc., Chem. Commun. 1979, 866.Miyaura, N.; Yamada, K.; Suzuki, A. Tetrahedron Lett. 1979, 3437Miyaura, N.; Ya

12、nagi, T.; Suzuki, A. Synth. Commun. 1981, 11, 513Negishi Coupling:Baba, S.; Negishi, E. J. Am. Chem. Soc. 1976, 98, 6729RX + RZnXRRNiCl2L2 (cat)Pd(0) (catalytic)Solvent/ LigandModern Organic Synthesis37Hiyama Coupling:RX + RSi(R)3RRLigand, ActivatorSolventPd(0) (catalytic)Hatanaka, Y.; Hiyama, J. Or

13、g. Chem. 1988, 53, 918Stille Coupling:RX + RSn(R)3RRLigand, BaseSolventPd(0) (catalytic)Kosugi, M.; Simizu, Y.; Migita, T. Chem. Lett. 1977, 1423Milstein, D.; Stille, J. K. J. Am. Chem. Soc. 1978, 100, 3636RX+RLigand, BaseSolventPd(0) (catalytic)Cu(I) (catalytic)RRSonogashira Coupling:Sonogashira, K

14、.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 4467Modern Organic Synthesis38Generalized Reaction Mechanism: Palladium CatalysisCross Coupling ReactionLnPd(0)RXOxidative AdditionRLnPdXRMTransmetallationRLnPdRMXR RReductive eliminationHeck ReactionLnPd(0)RXOxidative AdditionRLnPdXLnPd -H eliminat

15、ionRRRHRRHLnPdXBBHX-Modern Organic Synthesis39Challenge in the Activation of Inactive Chemical Bonds (C-X)I65 kcal/ molBr81 kcal/ molCl96 kcal/ molH113 kcal/ molSolutions to the Challenge in Palladium-Catalyzed Cross Coupling ReactionsElectron-Rich and Bulky Phosphorus LigandsRXOxidative Addition is

16、 facilitatedRLnPdXRMTransmetallationMXR RReductive elimination is facilitatedP Pd(0)Electronically RichP PdRRBulkyModern Organic Synthesis40Suzuki Coupling of Unactivated Aryl Chloride Catalyzed by PalladiumBr+BOOCO2EtBocHN5% PdCl2(PCy3)22 equiv CsFNMP, 100 oCCO2EtBocHNMeO41%OMeShen, W. Tetrahedron

17、Lett. 1997, 38, 5575Firooznia, F.; Gude, C.; Chan, K.; Satoh, Y. Tetrahedron Lett. 1998, 39, 3985Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1998, 120, 9722MeOCl +B(OH)22% Pd(OAc)23 % L3 equiv CsFdioxane, RTPCy2Me2NOMeLCl +B(OH)20.5-1.5% Pd(OAc)21-3 % L3 equiv CsF, THF, RTPtBu2LXYXYX

18、 = 4- Me, MeO, 2-MeO, 3,5-(OMe)2; Y = 3-COMe, H, 2-MeO88-98%Wolfe, J. P.; Buchwald, S. L. Angew. Chem. Int. Ed. 1999, 38, 2413Wolfe, J. P.; Singer, R. A.; Yang, B.-H.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 9550Modern Organic Synthesis41Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed. 1998, 37,

19、3387Cl+B(OH)21.5% Pd2(dba)33.6 % P(tBu)31.2 equiv Cs2CO3, dioxane, 80-90 oCXYXYX = 4- Me, MeO, NH2, 2-Me; Y = 4-CF3, H, MeO, 2-MeO, Me82-92%Cl+B(OH)21.5% Pd2(dba)33% P(tBu)33.0 equiv KF, THF, RT95%TfOMeTfOMeLittke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020Cl+B(OH)20.5-2.5% Pd2(dba)

20、31.0-5.0 % Ligand1.2 equiv CsF dioxane, 100 oCXYXYX = 4- MeO, 2-MeO; Y = 4-H, MeO, Me83-99%POButButHPOHButButLigandLi, Y.-G. Angew. Chem. Int. Ed. 2001, 40, 1513Modern Organic Synthesis42Cl+B(OH)22% Pd2(dba)34% LigandKOtBu, THF, 60 oCXYXYX = 4- MeO, Me, 2-Me, 2,6-(Me)2; Y = 2-Me70-95%NPNButtBuOHLiga

21、ndAckermann, L.; Born, R. Angew. Chem. Int. Ed. 2005, 44, 2444Cl+B(OH)2 Pd2(dba)3/LigandCs2CO3, Dioxane, 80 oCXYXYX = 4- MeO, Me, 2-Me, 2,5-(Me)2; Y =2-Me, 3-MeO, 4-MeO88-99%LigandNNClZhang, C.; Huang, J.; Trudell, M. L.; Nolan, S. P. J. Org. Chem. 1999, 64, 3804For a review, see: Wrtz, S.; Glorius,

22、 F. Acc. Chem. Res. 2008, 41, 1523ClNO2B(OH)2Ph+2% Pd2(dba)35 % Ligand2 equiv K3PO4Toluene, 70 oCNO2Ph83%, 72% eeNMe2PCy2LigandYin, J.; Buchwald, S. L. J. Am. Chem. Soc. 2000, 122, 12051Modern Organic Synthesis43Water-Soluble LigandsClR+ArB(OH)2Pd(OAc)2/LK2CO3, H2Ort-100 oCArRPCy2SO3NaOMeMeOL*HO2CHO

23、Me0.1% Pd, 100 oC, 96%H2NOCMe1% Pd, 100 oC, 99%MeMe2% Pd, RT, 96%MeMeMeH2NO2SF1% Pd, 100 oC, 96%FHO2C1% Pd, 100 oC, 93%NH2NH2HO2COHC1% Pd, 80 oC, 87%Anderson, K. W.; Buchwald, S. L. Angew. Chem. Int. Ed. 2005, 44, 6173Modern Organic Synthesis44Room Temperature Suzuki Coupling of Arylchloride with Po

24、lymer LigandsClR+ArB(OH)25 % Pd(OAc)2/LKF, THF, RTArRFePh2PORORORORPPh2FePPh2FeORORORORPh2PFeR = 4- MeO, Me; Ar = 2-MeC6H4, Ph38-75%Hu, Q.-S.; Lu, Y.; Tang, Z.-Y.; Yu, H.-B. J. Am. Chem. Soc. 2003, 125, 2856Disassociatation of Aryl-Oxygen BondOSO2Ar +B(OH)2 3 %Ni(COD)2/12% PPy3K3PO4, THF, RTXYXYX =

25、4- MeO, Me, 2-Me; Y = 2-Me, 4-MeO, MeAr = 4-MeC6H4, Ph86-99%Tang, Z.-Y.; Hu, Q.-S. J. Am. Chem. Soc. 2004, 126, 3058Modern Organic Synthesis45Cross-Coupling of Aryl Pivalates with Boronic Acids with Nickel ComplexesAr-OPiv+ArB(OH)25 mol% NiCl2(PPy3)2K3PO4, toluene, 110 oCArArBrOPivNBOO+Pd(PPh3)4, Ph

26、MeK3PO4, 90 oCOPivNSEMSEM5 mol% NiCl2(PPy3)2PhB(OH)2K3PO4, toluene, 110 oCPhNSEMOMe92%73%MeO2C92%PhOMeMeOMe65%OMe79%MeMeO65%NMePh82%OMe79%Quasdorf, K. W.; Tian, X.; Garg, N. K. J. Am. Chem. Soc. 2008, 130, 14422Modern Organic Synthesis46Total Synthesis of Quinine and QuinidineSynthetic ApproachNOHNO

27、MeHQuinineNNOMePgNOMeXNPgM+CNNHCO2MePgOOOPhNHOHNOMeQuinidineOPONHOPhEtOEtO+TBSOOHn-BuLi/THF-78-0 oCONHTBSOPhONCCO2Met-BuOH, C6H12, RTONHTBSOPhOCO2MeCN92% eeRaney-Ni, H2tol./MeOH (3/1)650 psi, 12 hNHOTBSOCO2MeNNOOtButButButBuAl(S,S)-(Salen)Al2O(Salen)AlModern Organic Synthesis47NHOCBzTPAP, NMOCH2Cl2N

28、OCBz+OBOCHCl2CrCl2, LiITHFNCBzBOONHOTBSOCO2Me(1) LAH, THF(2) CBz2O, TEA CH2Cl2NTBSOCBz(1) LDA, THF, -78 oC(2) H2O/THF, -78 oCNHOTBSOCO2Mecis/trans = 1/ 1.7cis/trans = 3/ 1OHTPAP, NMOCH2Cl2NTBSOCBzOCH3PPh3BrKOtBu, THF0 oCNTBSOCBzTBAFTHFNHOCBzModern Organic Synthesis48NCBzBOONHMeOOPh3PBr2Microwave170

29、oCNMeOBr+2.5 mol% Pd(OAc)2/ LK3PO4, THFNCBzNMeOMeOOMePCy2LADmix- , MeSO2NH2tBuOH, H2O, 0 oCNCBzNMeOHOOHMeOOMeMeOMeOBr(1)PPTS (cat), DCM(2)(3) K2CO3NCBzNMeOOEt2AlClthioanisole, 0 oCthen Microwave, 200 oCNOHNOMeHQuinineModern Organic Synthesis49NCBzNMeOADmix- , MeSO2NH2tBuOH, H2O, 0 oCNCBzNMeOHOOHNHOH

30、NOMeQuinidineRaheem, I. T.; Goodman, S. N.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 706Organotrifluoborates Participate in the Suzuki Coupling Reaction+BF3KClPd(OAc)2/ LK2CO3, MeOH50 oC, 20 h92%MeOOMePCy2LBarder, T. E.; Buchwald, S. L. Org. Lett. 2004, 6, 2649Modern Organic Synthesis50Stille Co

31、upling of Unactivated Aryl ChlorideClR+Bu3Sn-R1.5 % Pd2(dba)36% P(t-Bu)32.2 equiv CsF, Dioxane, 80-100 oCRRR = 4- MeO, NH2, n-Bu, 2,5-Me2;R = Ph, vinyl, 1-ethoxyvinyl, allyl, n-Bu61-98%Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed. 1999, 38, 2411Kumada Coupling of Unactivated Aryl ChlorideClR+n-PrMg

32、Cl0.1 % PdCl2(dppf)0.1%dppfTHF, 85 oCnPrRR = 2-Cl, 3-Cl, 4-Cl68-84%Katayama, T.; Umeno, M. Chem. Lett. 1991, 2073Modern Organic Synthesis51Kumada Coupling of Unactivated Aryl Chlorides with Pd-Carbene ComplexesClR+ArMgBr1 mol% Pd2(bda)34 mol% IPrHClDioxane/THF, 80 oCArRNNClIPrHClMe99%85%MeMeO97%Me87

33、%MeMeHO95%MeO99%MeMeMeMeO99%FMeMeO95%Huang, J.; Nolan, S. P. J. Am. Chem. Soc. 1999, 121, 9889Modern Organic Synthesis52Cl+MgX3 mol%Ni(acac)23 mol% L, THF, 20 oCXYXYX = 4- MeO, Me, 2-Me, 3-Me; Y = 4-MeO89-99%NPNOHLKumada Coupling of Unactivated Aryl Chlorides with Ni-Phosphine OxidesF+MgX3 mol%Ni(ac

34、ac)23 mol% L, THF, 20 oCXYXYX = 4- MeO, Me, 2-Me, 3-Me; Y = 4-MeO55-94%NPNOHLAckermann, L.; Born, R.; Spatz, J. H.; Meyer, D. Angew. Chem. Int. Ed. 2005, 44, 7216Modern Organic Synthesis53Kumada Coupling of Unactivated Aryl Chlorides with Iron complexesCl+MgX3 mol%FeF3, 9 mol% L18 mol% EtMgBr, 0 oCT

35、HF, 60 oCXYXY89-99%NNClL, SIPr.HCl98%F91%MeO92%MeMeOMe F81%OMeFMe90%OMeMeMeMe93%Bu87%F92%OMe96%OMe94%MeS80%Me2NNMeMeMe82%88%OOHatakeyama, T.; Nakamura, M. J. Am. Chem. Soc. 2007, 129, 9844For Iron Catalysis, see: Sherry, B. D.; Frstner, A. Acc. Chem. Res. 2008, 41, 1500Modern Organic Synthesis54Appl

36、ication of Iron-Catalyzed Coupling in Total Synthesis of isooncinotineNNHNOHH16101516IsooncinotineNNHNOHHHNHNOR1HNOOR2R2NHOONClClOR1BrMgSynthetic ApproachOBnBrMg+Fe(acac)3THF/NMP, 0 oCNClClOBnNCl83%Modern Organic Synthesis55NClOBn+NHOOCuI, DMEDAK2CO3, PhMe3140 oCNNOBnOO90%Pd(OH)2/CHOAc, MeOH35 oCNHO

37、H94% eeNHONNsBr+k2CO3, NaIEtOH, refluxNNHOHNOHNs(1) Swern Oxidation(2) Ph3PCH3Br, KHMDSNNHNOHNsHSCH2CO2HLiOH, DMFNNHHNOHMetathesisH2, 70 oCNNHNOHHScheiper, B.; Glorius, F.; Leitner, A.; Furstner, A. PNAS, 2004, 101, 11960Modern Organic Synthesis56Negishi Coupling of Unactivated Aryl ChloridesCl+ZnCl

38、Pd2dba3/ L (1 /2)THF, 70 oCXYXYi-PrOOi-PrPCy2L1% Pd, 93%iPriPrPriMe0.25% Pd, 97%iPriPrPriOMe0.1% Pd, 94%iPriPrPriCN0.1% Pd, 96%iPriPrPriOMe1% Pd, 76%NMe2OMe OMe0.25% Pd, 66%NMe2OMe CN1% Pd, 86%OMeOMe1% Pd, 83%OMeOMeMeMeMilne, J. E.; Buchwald, S. L. J. Am. Chem. Soc. 2004, 126, 13028Modern Organic Sy

39、nthesis57Heck Reaction of Unactivated Aryl ChloridesCl+1.5% Pd2dba36% P(t-Bu)31.1 equiv Cy2NMedioxane, 100-120 oCXXCO2MeMeCO2MeMeX = 4-MeO, 2-Me, 2,6-Me272-89% E/Z 20/1Littke, A. F.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 6989Hiyama Coupling of Aryl ChloridesSin-C5H11MeMeOK+ClRn-C5H11R2.5 mol% Pd(al

40、lyl)Cl25 mol% L, THF, 60 oCMeOOMePCy2LR = 4-Me, MeO, 2-Me, MeO, 2,6-Me289-95%E/Z 99:1SiMeMeOK+ClRn-C5H11R2.5 mol% Pd(allyl)Cl25 mol% L, THF, 60 oCR = 2-MeO, 2,6-Me287-98%Z/E 99:1n-C5H11Denmark, S. E.; Kallemeyn, J. M. J. Am. Chem. Soc. 2006, 128, 15958Modern Organic Synthesis58Cross Coupling Based o

41、n C-H ActivationNR+OBOBOBMeMeMe10 mol% Pd(OAc)2Benzoquinone (1 equiv)Cu(OAc)2CH2Cl2, air, 100 oCNRMeH38-93%RN+OBOBOBMeMeMe10 mol% Pd(OAc)2Benzoquinone (1 equiv)Cu(OAc)2CH2Cl2, air, 100 oCRNMeHNMe79%+NMeMe11%NMe50%+NMeMe20%MeMeNMe33%NMe70%NMe60%BuNMe50%MeOH2CNMe51%AcONMe70%MeO2CNMe22%Modern Organic S

42、ynthesis59Chen, X.; Goodhue, C.-E.; Yu, J.-Q. J. Am. Chem. Soc. 2005, 127, 6968NR+10 mol% Pd(OAc)2Benzoquinone (1 equiv)Ag2Otert-amyl alcoholair, 100 oCNRRHRB(OH)2NMeNEtNn-Bu67%64%75%Nn-C6H1351%N(CH2)2Ph53%N67%NNMeMeNBu43%n-Bu55%48%NMe40%NCyclopalladationPd(OAc)2NPd OAc2RB(OH)2NPdOAcRAg2ONR+Pd(0)Ben

43、zoquinonePd(II)Modern Organic Synthesis60Hiyama-Type ReactionHNR+5 mol% Pd(OAc)2Cu(OTf)2 (2 equiv)AgF (2 equiv)Dioxane, 110 oCNHRHOSi(OEt)3RROup to 80%HNRHOPdX2HNRPdOLXArSi(OEt)3FSiX(OEt)3-HNRPdOLArHNRArOPd(0)LnCu(OTf)2Yang, S.; Li, B.; Wan, X.; Shi, Z. J. Am. Chem. Soc. 2007, 129, 6066Modern Organi

44、c Synthesis61NClR1R25 mol% Pd(OAc)210 mol% LigandEt3N, C6H6, 100 oCR1NR2P(t-Bu)2Ligand60-97%NClPdLnNPdLnClNPdLnClHBorNPdLnClHBNPdLnHClHwang, S. J. Cho, S. H.; Chang, S. J. Am. Chem. Soc. 2008, 130, 16158Modern Organic Synthesis62Cleavage of Carbon-Carbon BondArCN+R1R210 mol% Ni(COD)220 mol% Me3Ptolu

45、ene, 100 oCR1R2CNArPrPrCNR54-96%PrPrCN61%PrPrCNN85%Met-BuCN59%, 99/1 rrMeO2CMei-PrCN84%, 62/38 rrMeO2CNakao, Y.; Oda, S.; Hiyama, T. J. Am. Chem. Soc. 2004, 126, 13904L2Ni(0)ArCNR1R2R1R2CNArNiL2NArNiLLCNArR1R2CNNiLLArLNiArCNLR1R2LNRModern Organic Synthesis63Cleavage of Carbon-Carbon Bond with Ni-LAA

46、rCN+R1R21 mol% Ni(COD)22 mol% PMe2Ph4 mol% AlMe2Cltoluene, 50-80 oCR1R2CNArup to 96%+PrPr2 mol% Ni(COD)24 mol% PMe34 mol% BPh3toluene, 80 oCPrPrCNup to 94%CNR2R3R1R1R2R3AlkylCN+R1R25 mol% Ni(COD)210 mol% PPh2(t-Bu)20 mol% AlMe3toluene, 80 oCR1R2CNAlkylup to 74%L2Ni(0)R CNR1R2R1R2CNRNiL2NRNiLLCNRR1R2

47、CNNiLLRLALALALNiRCNLLAR1R2LLANRNakao, Y.; Yada, A.; Ebata, S.; Hiyama, T. J. Am. Chem. Soc. 2007, 129, 2428Modern Organic Synthesis64Intramolecular Arylcyanation of AlkenesXCNRnR10 mol% Ni(COD)210 mol% PMe3, PMe2Ph, or DMPE20 mol% AlMe2Cl, toluene, 100 oCRXnRCNup to 96%CN10 mol% Ni(COD)210 mol% PMe3

48、,20 mol% AlMe2Cl,NiLCNLNiLLCNAlMe2ClLAProductCatalystSynthetic Application NCN10 mol% Ni(COD)220 mol% L*40 mol% AlMe2Cl,DME, 100 oCMeMeOMeONMeCN96% eePhIODCM, RTMeONMeCN40 %, 96% eeOLiAlH4, THF, RTthen refluxMeONNHMeMeHHCHONaBH(OAc)3MeOHMeONNMeMeHMeFeONPh2PL*Nakao, Y.; Hiyama, T.; Ogoshi, S. et al,

49、J. Am. Chem. Soc. 2008, 130, 12874Modern Organic Synthesis65Csp3-Csp3 Cross CouplingRakylXYZn Ralkyl+4 mol% Ni(COD)28% s-Bu-PyboxRakylRalkylDMA, RTNNNOOs-Bu-PyboxMeMeX = Br, 91%NTsX = Br, 66%OPhX = Br, 62%OEtEtEtX = I, 62%3OPhOOOX = I, 74%PhX = I, 73%NOOPhX = Br, 65%Zhou, J.; Fu, G. C. J. Am. Chem.

50、Soc. 2003, 125, 14726Modern Organic Synthesis66Asymmetric Catalytic Csp3-Csp3 Cross CouplingR2R3R1Cl+BrZn Ralkyl5 mol% NiCl2.glyme5.5 mol% (S)-BnCH2-Pybox4.0 equiv NaCl, DAM/DMF (1:1)-10 oCR2R3R1RalkylNNNOOBnBn(S)-BnCH2-Pyboxup to 98% eeSon, S.; Fu, G. C. J. Am. Chem. Soc. 2008, 130, 2756ArBrR1+9-BB