Direct, Iridium Catalyzed Enantioselective and Regioselective Allylic Etherification with Aliphatic AlcoholsSatoshi Ueno and John F. HartwigAngew. Chem. Int. Ed. 2008, 47, 1928Presentation by Nora JamesonChem 2320 02/18/08Ph OAcHO5 mol% [Ir / chiral ligand]20 mol% toluene, K3PO4, RT, 40hPh MePhOOverview•Allylic Substitution •Hartwig’s System•Side Reactions•Optimization•Substrate Scope•ConclusionAllylic Substitution•Tsuji-Trost reaction•Natural Product applications, Catalytic turnover•Intermolecular, metal additives, ROH poor Nu, elimination / catalyst poisoningXPdL2coordinationXPd(0)LLoxidative addition-X-Pd+LL(II)Pd+LL(II)-NuNuPd(0)LLNudecomplexation-PdL2Pd+LL(II)-NuPdLL(II)Nureductiveelimination-PdL2Nusoftnucleophiles:hardnucleophiles:Chem. Rev., 1996, 96, 395.Hartwig’s System•Ir metallacycle, 5 mol%, Cat formed in situ•Chiral ligands •Iridium processPhOAcHO Ph5 mol% (aR,R,R)-L15 mol% [{IrCl(cod)}2]toluene, K3PO4Ph Me,Ph Me,no40°C, 20h Rt, 40hPhO PhPhO Ph0% 64%68%traceOOPNPhPh(aR,R,R)-L1IrNPhPhL1POO[Ir(cod)(k2-L1)(L1)]OO(R)-binolSide Products: Enol Ether•Alkyne control•Effect on yieldOrg. Lett., 2006, 8, 6007. J. Am. Chem. Soc., 2003, 125, 13000.J. Am. Chem. Soc., 2006, 128, 4232.Ph OAc5 mol% (aR, R ,R)-L15 mol% [{IrCl(cod)}2]toluene, K3PO4Ph Me,Ph Me,no40°C, 20h Rt, 40hPhORPhORdisfavored favoredfavoreddisfavoredvs.ROHBranched or Linear•Selectivity of alkoxide addition•Polar solvents, thermodynamic / steric controlAngew. Chem. 2007, 119, 2132.Angew. Chem. Int. Ed., 2007, 46, 2086.Chem Commun. 2005, 1459.PhOAcHO5 mol% [Ir / chiral ligand]20 mol% toluene, K3PO4, RT, 40hPh MePhOvs.Ph OOptimization •Ligand•Solvent•Base: trans esterification, NEt3L1L2L3L4L5L6R1 = PhR1 = 2-anisylR1 = 1-NpR2 = PhR2 = 2-anisylR2 = 1-Np91:995:587:1390:1082:888:12736264645960959991918971LLigandBranched:LinearYield [%] ee [%]OOPNR1R1OOPNcC12R2PhOAcHO5 mol% [Ir / chiral ligand]20 mol% toluene, K3PO4, RT, 40hPh MePhOorPh OScope•BnOH, 2’ROH, NBocROH, *2’ROH, R3SiOH, •with High ee, High de•Tertiary alkoxides•Decarboxylative etherificationPhO10 mol% (aR,R,R)-L15 mol% [{IrCl(cod)}2]toluene, K3PO4PhOOOPhPh48%, 84% ee2.5 mol% (aR,R,R )-L11.25 mol% [{IrCl(cod)}2]toluene, K3PO456%, 97% eeO PhMeOOAcMeOHO PhO PhOO PhMeOO PhO PhOMeOOMeOPhONBoc82%, 92% eeb:l = 99:167%, 93% eeb:l = 96:468%, 84% eeb:l = 99:157%, 93% eeb:l = 82:1875%, 94% eeb:l = 99:183%, 96% deb:l = 99:140%, 94% eeb:l = 99:1Angew. Chem. 2006, 118, 6350.Angew. Chem. Int. Ed., 2006, 45, 6204.Conclusions•Highly regio and enantioselective Ir-catalyzed allylation•Controlled isomerization•Broad substrate scope with various ROH’s•First 3’ allylation•First asymmetric decarboxylative allylation with O-nucleophileAny
View Full Document
Unlocking...