金属催化C-O键形成合成二芳基醚的研究进展课件.ppt

1、金属催化金属催化C-OC-O键形成合成二芳基醚的研究进展键形成合成二芳基醚的研究进展主要内容：1.引言2.铜催化的Ullmann偶联反应合成二芳基醚3.铜催化芳基硼酸的偶联反应合成二芳基醚4.钯催化的Buchwald-Hartwig反应合成二芳基醚5.小结二芳基醚是生命科学研究中非常重要的一类有机化合物，该结构单元存在于多种天然产物和具有生理活性的化合物中。1.铜催化的Ullmann偶联反应2.铜催化芳基硼酸的偶联反应3.钯催化的Buchwald-Hartwig反应4.亲核取代反应5.氧化偶联反应概述：For reviews,see:1)Tetrahedron 1984,40,1433.2)T

2、etrahedron 2000,56,5045.铜催化的Ullmann偶联反应合成二芳基醚Buchwald,S.L.et al J.Am.Chem.Soc.1997,119,10539.XR1HOR2+2.5 mol%(CuOTf)2PhH5 mol%EtOAcCs2CO3,toluene110 oC1-naphthoic acidX=Br,I76-93%yield12-26 hR1=Me,CN,OMe,AcR2=Me,i-Pr,ClOR1R2OMeMeMeOCOOHMeMe85%yield84%yieldOMe79%yieldOMe铜催化的Ullmann偶联反应合成二芳基醚IR1HOR2+C

3、uBr(2 equiv)toluene,110 oCP4-But(2 equiv)OR1R2OMeMe72%yield81%yieldMeMeOMeMeOMe70%yieldOMeMeOPalomo,C.et al Cmun.1998,2091.56-81%yieldR1=Me,MeO,Cl,CN,AcR2=Me,t-Bu,MeOBrR1HOR2+Cu(neocup)(PPh3)BrCs2CO3,toluene(10 mol%)110 oC,36 hOR1R231-99%yieldR1=Me,H,NO2,AcR2=Me,H铜催化的Ullmann偶联反应合成二芳基醚NNCuPh3PBrNNCuP

4、h3PBrCu(neocup)(PPh3)BrCu(phen)(PPh3)BrVenkataraman,D.et al Org.Lett.2001,3,4315.31%yieldOMeMe铜催化的Ullmann偶联反应合成二芳基醚XR1HOR2+CuCl(50 mol%)Cs2CO3(2 equiv)NMP,120 oC,1.5-47 hX=Br,ITMHD(10 mol%)OR1R251-82%yieldR1=Me,NMe2,NO2,Ac,CNR2=Me,OMe,F,CO2i-PrOOTMHD51%yieldOCO2i-PrMeOOFAc61%yieldOFMeO55%yieldSong,Z

5、.G.et al Org.Lett.2002,4,1623.铜催化的Ullmann偶联反应合成二芳基醚XR1HOR2+CuI(4 mol%)Cs2CO3(2 equiv)90 oC,dioxane,4-24 hX=Br,IN,N-dimethylglycine HCl salt(15 mol%)OR1R233-96%yieldR1=Me,OMe,NHBn,CNR2=Me,OMe,t-BuMa,D.et al Org.Lett.2003,5,3799.OOMe59%yield(90 oC)75%yield(105 oC)MeOMeMeO33%yield(90 oC)64%yield(105 oC

6、)OOMe56%yield(4 mol%CuI)80%yield (100 mol%CuI)铜催化的Ullmann偶联反应合成二芳基醚BrYHNHOR2+CuI(30 mol%)Cs2CO3(1.5 equiv)rt,dioxane,3-14 hN,N-dimethylglycine(15 mol%)OYHNR251-90%yieldO51%yieldNHCOCF3CO2MeNHCbzCO2MeONHCOCF3Me82%yieldO81%yieldNHCOCF3BrNMeBocCO2MeMa,D.et al Angew.Chem.Int.Ed.2006,45,1276.Y=COCF3 COCH

7、3 COPh SO2Me铜催化芳基硼酸的偶联反应合成二芳基醚B(OH)2R1HOR2+Cu(OAc)2(1 equiv)CH2Cl2,25 oC,18 hEt3N or pyridine(5 equiv)in airOR1R2up to 98%yieldR1=H,F,Me,MeO,ClR2=MeO,t-BuO68%yieldOMeCO2MeNHBocO7%yieldClCO2MeNHBocO42%yieldt-BuFEvans,D.A.et al Tetrahedron.Lett.1998,39,2937.铜催化芳基硼酸的偶联反应合成二芳基醚B(OH)2R1HOR2+Cu(OAc)2(1-2

8、equiv)CH2Cl2,25 oC,24-72 hEt3N or pyridine(2-3 equiv)in airOR1R2OR=Me,73%yieldR=H,40%yieldR=OMe,73%yieldRt-But-BuOFICl78%yieldChan,D.M.T.et al Tetrahedron.Lett.1998,39,2933.铜催化芳基硼酸的偶联反应合成二芳基醚Ot-But-BuB(OH)2HOt-But-Bu+Cu(OAc)2(10 mol%)1.1 eq oxidantCH2Cl2,4A MSpyridineB(OH)2HOt-But-Bu+Cu(OAc)2(10 mol

9、%)1.1 eq oxidantCH2Cl2,4A MSPhEt3NPhOt-But-BuO2,50 oC,79%yieldTEMPO and air,50 oC,16%yieldPyridine N-oxide and air,50 oC,9%yieldO2,50 oC,22%yieldTEMPO and air,50 oC,23%yieldPyridine N-oxide and air,50 oC,13%yieldCu(OAc)2(1.1 eq)in air,rt,67%yieldLam,P.Y.S.et al Tetrahedron.Lett.2001,42,3415.铜催化芳基硼酸的

10、偶联反应合成二芳基醚Ot-But-BuHOt-But-Bu+Cu(OAc)2(1 eq)CH2Cl2,rt,24 hEt3N or pyridine(2 eq)BORROChan,D.M.T.et al Tetrahedron.Lett.2003,44,3863.PhB(OH)2(PhBO)3PhB(Oi-Pr)2PhBOOPhBOOPhBOOPhBOOPhBOOMeMeMeMe17%43%39%29%21%32%18%4%钯催化的Buchwald-Hartwig偶联反应合成二芳基醚XR1NaOR2+Pd(dba)2(2-5 mol%)Ligand(2-5 mol%)toluene,80-11

11、0 oC9-24 hX=Cl,BrOR1R263-85%yieldR1=Me,t-Bu,BzR2=Me,OMeFeP(t-Bu)2ligand85%yieldOOMe74%yieldOOMet-Bu81%yieldOOMeHartwig,J.F.et al J.Am.Chem.Soc.1999,121,3224.钯催化的Buchwald-Hartwig偶联反应合成二芳基醚XR1NaOR2+Pd(dba)2(5 mol%)OR2R1Ligand(5 mol%)toluene,rt or 80 oC4-70 hX=Cl,BrFeP(t-Bu)2ligandPhPhPhPhPhup to 99%yi

12、eldR1=OMe,H,Me,Bz,NO2R2=H,Me,OMe,NO2,OTBSORR=t-Bu,rt,14 h,79%R=TBS,rt,16 h,99%R=4-MeOC6H4,rt,70 h,99%Onn=1,rt,5 h,59%n=2,rt,0.5 h,64%Onn=1,rt,15 h,77%n=2,rt,10 min,64%Hartwig,J.F.et al J.Am.Chem.Soc.2000,122,10718.钯催化的Buchwald-Hartwig偶联反应合成二芳基醚XR1HOR2+Pd(OAc)2(2 mol%)Ligand(3 mol%)toluene,100 oC14-2

13、6hX=Cl,Br,OTfK3PO4(2 equiv)OR1R261-96%yieldR1=OMe,t-Bu,Ac,CO2Me,CN,ClR2=H,Me,OMe,t-BuBuchwald,S.L.et al J.Am.Chem.Soc.1999,121,4369.P(t-Bu)21P(t-Bu)22P(1-Adamantyl)23PhP(t-Bu)24NMe2钯催化的Buchwald-Hartwig偶联反应合成二芳基醚XR1HOR2+Pd(OAc)2(1-3 mol%)Ligand(3 mol%)toluene,100 oC5-24 hX=Cl,BrK3PO4(2 equiv)OR1R2up

14、to 94%yieldR1=CN,Ac,CF3,CO2Me;Me,MeO,NMe2,NHCOMeR2=H,Me,CN,CO2Mei-Pr6P(t-Bu)2i-Pri-Pri-Pr7P(t-Bu)2i-Pri-PrMeMeMeMei-Pr8P(t-Bu)2MeBuchwald,S.L.et al Angew.Chem.Int.Ed.2006,45,4321.Buchwald,S.L.et al Angew.Chem.Int.Ed.2006,45,4321.钯催化的Buchwald-Hartwig偶联反应合成二芳基醚OMei-Pr84%Oi-PrMeO74%O84%Me2NNOi-Pr90%NOM

15、e88%NNOMe87%钯催化的Buchwald-Hartwig偶联反应合成二芳基醚ClR1HOR2+Pd(OAc)2(2 mol%)Ligand(4 mol%)toluene,120 oC,20 hK3PO4(2 equiv)OR1R2up to 99%yieldR1=CN,Ac,CF3,Me,MeO,ClR2=H,MeNPhPAd2NPhP(t-Bu)2OMeO87%yieldOMeO68%yieldO92%yieldBell,M.et al Tetrahedron.Lett.2005,46,3237.小结及展望铜催化的Ullmann偶联反应：催化剂廉价，用量低，底物范围广；条件苛刻等铜催化芳基硼酸的偶联反应：催化剂用量高，条件温和；底物范围窄等钯催化的Buchwald-Hartwig反应：催化剂用量低，底物范围广，条件温和；催化剂价格昂贵（金属、膦配体）发展高效、廉价、条件温和、底物适用范围更广的催化体系仍然是金属催化C-O键形成合成二芳基醚的研究方向。