Jimin KimThe Sorensen Group, Department of ChemistryJimin KimThe Sorensen Group, Department of ChemistryAugust 23, 2006Allenes as Products, Substrates, or IntermediatesinOrganometallic TransformationsStructure of AlleneAllenes: 1,2-dienyl compounds with stereogenic axisIn 1875, Van’t Hoff had expected an allene structureIn 1887, Burton and von Pechmann reported the first documented synthesisCH3HHH3CH3CHHCH3Chirality of Allene(M)-2,3-pentadiene(P)-2,3-pentadieneStereogenic AxisHCH3Counter-clockwiseMClockwisePHCH3HH3CHH3CNatural AllenesRepresentative natural products containing an allene moietyHoffmann-Roder, A.; Krause, N. Angew. Chem. Int. Ed. 2004, 43, 1196.nC8H17HHMegatomoic Methyl EsterMe MeOOOOOHOHHOHOOHHMeOHHMeOHOCinnamosideOOHHBrHHHBrClHNH2HOOHOOMeAcOHHHAcOHHGinamalleneObtusallene4,5-Dienoic aminoacidHOOHHHHBrHBrHKumausalleneHNHOIsodihydrohistrionicotoxinMe MeAcOMeOHHMeMeOOMe OHMe MeOPeridininisolation 1890; structure 1971; synthesis 2002CO2MePreparation MethodsXHIsomerization ReactionsXbaseMostlyX = O, N, P, S, R-CO, C=C, Si, SnE (Kcal/mol)+2.1+20.2RHO HCH2O, iPr2NHCuBr, dioxaneCrabbe Homologative AllenylationRHO HHSimple trial with many functional groupstoleranceR'O HORi. LDA ii. TMSCliii. 67oC iv. CH2N2R'HRCO2MeClaisen ProtocolSigmatropic RearrangementsA variety of[2,3]-Wittig, [2,3]-Sigmatropics are well establishedMsO HR2CuLiHRHMetal Mediated SN2' Type SubstitutionsVarious nucleophiles and metals have been utilizedfor this transformationπ-Facial Aspects of SN2’Self-immolative chirality trasfer from center to axis chiralityXR2R1HXR2R1HNuanti-modeNusyn-modeBoth modes are stereoelectronically allowedR1HNuHR1HHNuπ∗σ∗XHN, O, S nucleophilecuprate, Pd, Ni...d-block elementsSyn-substitutionNuAnti-substitutionNuSN2'In general,Syn SN2’ DisplacementOHN HN HCOPhCl2NOCOPhCl2HSynantiNOHCOPhCl2diaxial..π−πwell overlap!Hcan't interactNNChairTwist"Stereoelectronic Effects in Organic Chemistry"Deslongchamps, P. Pergamon, 1983, pp.174-178.Mechanistic Aspects of Syn SN2' ReactionOOPhCl2NHOOPhCl2NHNNSynSynStork, G. et al., J. Am. Chem. Soc. 1953, 75, 4119; 1977, 99, 3850Anti SN2’ DisplacementCombineMechanistic Behavior of anti-SN2' substitution of Proparylic XOrganocuprate and Organocopper CompoundsXantiRCu-LCuIIIRLRCu-LCuR LCuRanti-SN2' displacement of allylicXsyn-addition to triple bond−CuL−XsynRXHR1RCuX MgXCuXHR1RXCuXHR1RXHH−XCuIIIHHR1RX−CuXreductiveeliminationRHHR1Corey, E. J.; Boaz, N. W. Tetrahedron Lett. 1984, 25, 3063.Elsevior, C. J.; Vermer, P. J. Org. Chem. 1989, 54, 3726.Krause, N. Ed., "Mordern Organocopper Chemistry" Wiley-VCH, 2002.MgXAnti vs Syn SelectivityOMeBuHBuMgXCuBr (5 mol%)P(OEt)3Et2OX = IX = ClBuHBuHanti : syn = 98 : 2anti : syn = 20 : 80BuHHBuBuMgXCuBr (5 mol%)PBu3, Et2OX = BrX = Clanti : syn = 100 : 0anti : syn =12 : 88OCuBr (5 mol%)Me3SiCl, Et2OOHBuHOHHBu(without TMSCl, 35 : 65)Alexakis, A. et al. J. Am. Chem. Soc. 1990, 112, 8042; Tetrahedron 1991, 47, 1677.Plausible PathwaysOMeBuBuCuBr MgXBuHCuMeOBuHBr MgXanti-eliminationBuHBuHX = I favorBuMgX + CuBrδ+δ−+ MeOMgXetherδ+δ−etherHδ+δ−etherBuHHBuMgX2X = Cl favorBuHMgOHBu- CuBrClMeMgClClsyn-elimination+ MeOMgXR2Mg + MgX22 RMgXKK = I > Br > ClTHF >> ether1) Schlenk Favor?2) Only for Cl?OOMgClHBuOCu BuXMg BrBuCuBr MgXOMgXBuHX = Br favorX = Cl favorMgCl2OHMgClMgClClantisynOSiMe3HBuMe3SiClincrease MgCl2enhance syn selectivityBuSN2’: C-C Bond FormationOTBSTHPOOPhOTHPOHH1) CBr4, PPh32)CuCO2MeOTBSTHPOOPhOTHPHHCO2MeHOOPhOHHHCO2HOEnprostilCooper, G. F. et al. J. Org. Chem. 1993, 58, 4280.NSOOHOAcPh2CHO2C1)MgBr2) Tf2O, pyrNSOHOAcPh2CHO2CTfO2 tBuLi, CuCNNSOHOAcPh2CHO2CHtBuBuyanak, J. D. et al. J. Am. Chem. Soc. 1994, 116, 10955.SN2’: C-X Bond FormationCrimmins, M. T.; Emmitte, K. A.. J. Am. Chem. Soc. 2001, 123, 1533.OOHHEtTESOHOH1) Sharpless2) PPh3, NCSOOHHEtTESOHCl1) LDA2) ArSO2ClOOOHHEtTESOHOSO2ArLiCuBr267%OOHHEtTESOHBrH1) PPTS, MeOH2) CBr4, Oct3POOHHEtHBrHHHBrPhMeOTsOMeLiCuBr275%PhOMeHMeBrMeCu(CN)LiPhMeMeOMeMeO2CSnMe3MeNHBoc1) Cp2ZrHCl, then I22) PdCl2(MeCN)23) LiOH, then H3O+HO2CMeNHBocPhMe MeOMeN-Boc-ADDA(-)-IsolauralleneD'Aniello, F. Mann, A.; Taddei, M. J. Org. Chem. 1996, 61, 4870.SN2’: C-H Bond FormationMaumeler, A. et al. Hel. Chim. Acta 1990, 73, 700.Et3SiO MeOMeOHMe MeDibal-HEt3SiO MeOMeOAlMe MeAlHiBuiBuSynEt3SiO MeOHMe MeHMeOH1) MnO22) H3O+HO MeOHMe MeHMeOGrasshopper ketoneOHTHPOHRLiAlH4AlOHTHPOHRHHLiAntiHROHHBerger, A. et al. Synthesis 1989, 93.R1HR2OHNBSHPh3P,DEADR1R2HNNHHSO2ArHR1R2HSynMyers, A.; Zheng, B. J. Am. Chem. Soc. 1996, 118, 4492.; Kitching, W. J. Org. Chem. 2003, 68, 3739.-NO2PhSO2HR1R2HNNH- N2Pd Catalyzed ReactionsR1XR2HPd(O)R1PdIIXLLR2HPhZnCl2, iPr2NHCuIAntiR1R2HPh85% ee from 93% eeChem. Commun. 1997, 2083.X = OCO2Me, Pd(PPh3)4CO (200 psi)rt, MeOH/THFX = OMs, Pd2(dba)3, PPh3R1R2HMeOO70% ee from 80% eeLiEt3BH X = OMs, Pd(PPh3)4R1HR2H49% ee from 58% eeTetrahedron Lett. 1984, 25, 845.J. Org. Chem. 1997, 62, 367.Pd Catalyzed Allylic SubstitutionnC8H17BrPd(dba)2 (10 mol%)H2C(CO2Me)2, CsOtBu(R)-segphosnC8H17PdPP*77% eenC8H17HCO2MeCO2MeHOOOOPPh2PPh21) KOH, then H3O+, 100 oC2) CH2N2nC8H17HCO2MeH(R)-segphos1) LDA, then PhSeBr2) NaIO4nC8H17HCO2MeHHHDried bean beetleHayashi, T. et al. J. Org. Chem. 2005, 70, 5767.Also see, J. Am. Chem. Soc. 2001, 123, 2089.Org. Lett. 2003, 5, 217.Reactions of Allenes: General Survey Ma, S. Chem. Rev. 2005, 105, 2829-2871.CycloadditionOCO2MeOHOHCO2MeOOHOHHA variety of [4+2], [3+3]cycloaddition reactionsR1R2HCO2EtOxidation--Oxo transferVersatile substrate for oxidationsR3RuCl3(cat)NaIO4R2CO2EtOH OHR3R1OTM Catalyzed Addition to AllenesVarious transition metal catalyzedcycloisomerization of allenesTsNOHTsNOOHHRu3CO12CO, Et3NMetal Mediated Ionic ReactionsAs a unique substratefor many metallic cationsHONMeHOHBocOMeONBocHPdII,AgI, AuIActivating Metals for AllenesMNuNuMNu = O, N, C, S, XM = Pd, Ag, AuPdRh, Hg, Cu, Ce, Fp+, etcPtAgAu10 11More electronegative...more covalent character with COSENII,IIIII,IVII,IV2.541.932.202.28 Natural adundant MoreLessOxidation Stateusually IIAu I, III are capable of catalizing the same transformationRedoxRe OxRe OxXβ-HeliminationYes No, usually proto-demetallation--charateristic!Hoffmann-Roder, A.; Krause, N. “The Golden Gate to Catalysis” Org. Biol. Chem. 2005, 3, 387-391 and references cited therein.Regiochemical CoursesType IIMetalNuNu M = R-PdIIMAr-X + Pd(0)PdXArMigratoryinsertionArPdIINu'ArNu'Type IMetalNuNuMM = AgI, AuI,III,PdIIHOnn = 1,2OM+MHHδ+allylic >> vinylic