1、第五章第五章 p p- -烯丙基金属和炔丙基金属化学烯丙基金属和炔丙基金属化学 5.15.1 烯丙基钯化学烯丙基钯化学 5.1.1 p5.1.1 p-烯丙基钯络合物的制备 SiR3PdLi2PdCl4+CH2=CHCH3+(R3Si)2O1(1)Cl2THF, H2O(CH2=CHCH2)2O+PdCl42-+CH2=CHCHO(2)PdClClaq. MeOHRRPdRR+PdCl2+ HCl2(3)Cl2+ PdCl2 + X-X = Nucleophiles, Cl, OCH3, OAc3(4)PdCl2XPdClClCH2=C=CH2+PdCl2+46(5)5PdCl2PdCl2ClC
2、lPhPdPhPh+ PdCl2(PhCN)278(6)PhPhCl2ClPhXPdXXPdXPdPd(0)(7)X=Br, Cl1A5.1.2 p-烯丙基钯络合物的反应 H2O(8)CH2=CHCH2COORH2C=CHCCNRORPdCl21. RNC2. ROH+ CO + ROHCH2=CHCH2CO2R + Pd + HCl(9)PdCl2+ CH3COCH2COORBaseCH(COCH3)CO2R9(10)PdCl2Pd-LnPdNuNu-Pd(0)Nu(11)Nu=R1R2OMeOTMSLn 5.25.2 钯催化的烯丙基类化合物的反应钯催化的烯丙基类化合物的反应 RYRMYRY
3、M(0)(12)PdORRRLH+ Pd(0)Lm(13)RORRPdORLRORRPdHLRorPd (0)HCO2-R. E.+ Pd (0)CO210RRRSOORRRRSROORSOOPd(PPh3)4THF+(15)OXOXPtOXPt (0)+Pt (0)(14)R3R4OPR1R2R3R4OPR2R1R3R4OPR2R1+Ni(COD)2(16)OCSRMOCSRMSRM (0)+_- COS+- SRSSR1OSR3R2SR1SSR3R2OR1R2SR3R2R1R3SorPd(PPh3)4 / dppeTHF, 20 - 65 oC- COS50 - 86%+ROOOROOOR
4、OOPdOROPdROor- CO2R. E.111213OCO2R1R2R1O PdR1R2OPdPPh3141516R25.3 5.3 钯催化的烯丙基化合物的亲核取代反应钯催化的烯丙基化合物的亲核取代反应 Y = RCO2-, ROCO2-, RO-, (RO)2P(O)O-, R2N-, -NO2, -SO2R, -NR3X, -SR, -P(OR)2, -As(OR)2, -B(OR)2, -OC(S)SRRYRPdYRNuPd(0)Nu-+ Pd(0)CO2OCO2MeOCOOOOCO2OPd-OMeCO217181920aCO2OPd+R2CHR1OHClCOOR2CHR1OCO2
5、R2CR1OPdHR2CR1OHPdH+ Pd (0)Pd (O)- CO22122232425OHOAcXYROXYXY+1. Pd (0)2. Ac2O1. NaH2. PdL4262728 R=H29 R=Ac30OOE1E1OE2E2E1E1OONR1AcOOAcE2E2OE = CO2EtE = CO2MePd(PPh3)4PPh3,BSAPd(PPh3)4dppe, BSA1. Pd(0)2. H2O+31323436373533R1ONHOCOOMeOMeNOMeOCH2MeOOCNOMeOCH3MeOOCNHOCH3H2NH3CHuperzine A38394041ROAcOA
6、c+CH(CO2Et)2Pd(0)OOAcCOOEtCOOEtR+ROOAcCOOEtCOOEt45424344ROAcOAc+Pd(0)42ROPd+LLCH(CO2Et)2RHO+OCO2EtCO2Et464748OTMS OAcEWGEWGPd (O)505449TMSPd+-OAcLL51Pd+LL52Pd+LL53EWGTMS OAcOO+Pd(0)5556PhO2SRYXOAcXYPhO2SRXYPhO2SRBaseand / or575859RXYCO2CH3C = OPd(PPh3)4Pd(PPh3)4Pd(dppe)2CO2CH3PhSO2CH2CH2CH2CH2OA)B)C
7、)onlyonlyonly5859OOOOCOOHOOSO2PhOEtOOOC2H5OAcOPhO2SAntibiotic A26771B15HNONOHNONOH2NONOAcOInandenin - 12 - one1. 10 mol% Pd(PPh3)4 8 mol% dppb 2. THF NaHCO3NHAcNHAcNHAcNuOCO2ROCO2RPd (0)Pd +Nu -Pd +NuH- ORROHCO2Pd +_E2E1OCO2RE1HPd+E1E1E2E1E2Pd (0)ROHCO2- ORPd606162636465MeO2COCNOOCN+Pd2(dba)3.CHCl3T
8、HF, reflux71%OCO2ROSiMe3O - PdOPd (0)ROSiMe3Pd +- OR66676869OCO2MeO - PdOOAcOSnBu3Pd (0)CO2MeOSnBu3AcOMeOCO2MeClOPhOOPhCO2MeOCO2MeCOOMeOOCOOMe+Pd(OAc)2PPh377%Pd(OAc)2P(OPh)3,CH3CN66%70717273OCOOMe73195 , 43%OSO2TolC5H11OOHHOOPOOSO2TolC5H11OOHHHPdLnOSO2TolOPdLnC5H11OHHHOSO2TolOC5H11OHHHOSO2TolOC5H11O
9、THPHOOROCNC5H11OTHPHOOTsOC5H11OHHCOOHOPd2(TBAA)3, CHCl3_+747576777879805.4 5.4 p p- -烯丙基钯接受亲核进攻反应中的立体化学烯丙基钯接受亲核进攻反应中的立体化学 COOMeOAcCOOMeSnBu3COOMeDBu3SnAlEt2cat. Pd(PPh3)4/PPh3cat. Pd(PPh3)4/PPh3NaBD4818283COOMeOAcCOOMePd+L2COOMeCH(COOMe)2COOMeOAcCOOMeOAcCOOMeCH(COOMe)2COOMeCH(COOMe)2inversioninversi
10、onNaCH(COOMe)2cat. (PPh3)4Pd/PPh3THF reflux 92%NaCH(COOMe)2cat. (PPh3)4Pd/PPh3THF reflux 92%Soft nucleophilesafford overall retention ofstereochemistry8184858681RPdLL+FavouredsynDisfavouredantiPdLL+RFavouredsyn, synDisfavouredanti, antiRPdLL+PdLL+RRRMeOAcPhPhOAcMePhCH(COOMe)2MePhCH(COOMe)2MeOAcPhPhO
11、AcMePhPhPd+L2Pd+MePhPd+L293L29192NaCH(COOMe)2cat. Pd(0)+90:1087899088 5.5 5.5 p p- -烯丙基钯中间体的不对称亲核取代反应烯丙基钯中间体的不对称亲核取代反应OOOOPh+Pd2(dba)3 CHCl3(+) - BINAPBSA, THF60 oC73% yield, 92% ee(16)PhPhOAcPhPhPdLLabPh*949596OAcCO2CH3H3CO2CCH3H+Na CH3C (CO2CH3)293% yield, 87% ee(17)2.5 mol% Pd2(dba)3.CHCl35 mol%
12、97, THF, rtPh2P97PPh2NHOHNOOC(CH3)3OOCO2CH3OCO2CH3(CH3)3CCOONa(C6H13)4NBrCH2Cl2, -78oC98, C3H5PdCl291%, 97% ee+ref. 43ONH HNOPh2PPPh298ICOOHOO+10% 99Ag3PO4 , DMF, 40oC52%, 61% eeref. 445 mol% Pd2(dba)3.CHCl3NNOOBnBn99XHNHRYYXNR+(R) - BINAPTHFR = PhCH2, X = O, Y = OAc, 44%, 64% eeR = Ts, X = NTs, Y =
13、 OCO2Me, 74%, 60% eePdref. 45*OCO2CH3OAcCO2CH3OCO2CH3CO2CH3H100, THFref. 4634%, 83% eePd(OAc)2-2BuLiLiOAcPPh2PPh2NFe100OOOAcOO+92% yield, 75% ee0.5 mol% Pd2dba3.CHCl31.1 mol% 101, KF47PPh2PPh2NOONONOFe101MePhOCOOEtPhPhNHCH2PhPh1.5 mol% Pd2(dba)34.5 mol% ligand 9240 oC / THF /PhCH2NH2rac93PPh2MeNR1R2
14、NFe(S)-(R)-92FePPhNNPhR1PdPhPh+exo-syn-syn-94FePPhNNPhR1PdPhPh+exo-syn-anti-95R2R292a R1 = 1-adamantyl92b R1 =92c R1 =R-93S-93ee 99% (R)40% (S)NRXPhMgBrPhMgBrPh+50%, 31% ee106 NiCl2ether, refluxX = OPh 50% (31% ee)X = Br 50% (55% ee)PPPhPhPhPh106PhOOOOPhPhOONHBocONHBocONHBocBrNCl(C4H9)3SnONHBocNClON
15、HBocNClOHNHBocNClNClNHa81%b90%c80%de76%f67%g45%(-)-epibatidine反应条件反应条件: (i) 0.25 mol% 3-C3H5PdCl2, 0.75% mol% cyclohexyl ligand, 1.2equiv. TMSN3, THF, 0 oC; (ii) (CH3)3P, 2:1 THF-H2O, 1.2 equiv. (CH3)3P, rt then add (t-C4H9OCO)2O, NEt3. (b) K2CO3, CH3OH, rt then Dess-Martin periodinane, CH2Cl2, rt (
16、c) Br2, NEt3, CH2Cl2, 0 oC. (d) 2.5 mol% Pd(dba)3.CHCl3, 15 mol% AsPh3, THF, 55 oC. (e) K-selectride, THF, -78 oC to 0 oC then cat. DBU, THF. (f) NaBH4, CH3OH, 0 oC. (g) CH3SO2Cl, NEt3, CH2Cl2, 0 oC; CF3COOH, H2O, rt; CH3CN, reflux.OHNOONOOOH(3-C3H5PdCl)2, Na2CO3, CH2Cl2, rt+107PPh2NHOHNOPh2PNOOOHHN
17、OOXHNOOHCO2CH3CO2CH3NH3ClHCO2HX=OTs, I, OTf5.65.6 其它其它 3 3- -烯丙基金属烯丙基金属1/3-1/3-位碳接受亲核进攻的反应位碳接受亲核进攻的反应 5.6.1 3-烯丙基镍 POAcOR2R1108P H/NiCl2OR3R4BSA110-130oC, 10.5-20hP OR5/NiCl2OR3R4110-120oC, 3-24hPOR2R1109POR4R3POR2R1110POR4R3+(18)major或Br+Ni(CO)4NiBrBrNiNi+NiBr2Br100%BrBr111Ni(CO)4112BrBr113Ni(CO)41
18、14(allyl)NiBr+RXSET(allyl)NiBr+RXRXR+XR+(allyl)NiBrR-allyl+NiBrNiBr+RXRX+NiBrNiBr+OOOO(19)1151161175.6.2 烯丙基钼 H3CO2CRCO2CH3OAcNaCR(COOCH3)2Pd(PPh3)4CO2CH3CO2CH3CO2CH3CO2CH3R=H 119aR=CH3 119b118120119aOAc118NaCH(COOCH3)2Mo(CO)6Mo(CO)6NaCCH3(COOCH3)2H3C(H2C)15CO2CH3OAccat.Mo(CO)6BSAPhCH3H3C(H2C)14CO2C
19、H3(CH3)2AlNH3C(H2C)14NO121122123CO2CH3OAC+Al(TMS)3Mo(CO)6PhCH3CO2CH3TMS(20)1241255.6.3 烯丙基钨 PhOCO2CH3126+NaRC(CO2CH3)2THFPhCO2CH3RCO2CH3127(21)OOCO2CH3128+H3CO2CCO2CH3129cat. W(0)OCO2CH3CO2CH3130(22)(MeCN)3W(CO)3, bpyR = H or Me5.7 5.7 中间碳接受亲核进攻的中间碳接受亲核进攻的p p- -烯丙基金属化学烯丙基金属化学PdCl2+COOMe2 PPh325 oC20
20、%Et3NTHF-HMPA-78oC to 25oC131132COOMe133COOMe13470%PdCl2136PhPhNOPhPh+LDATMEDATHF, CO -35oC135NOPhPh137PhPh65%(23)PdCl2136PhPh1. TMEDA2.CNNPdNCNPhPhCOCNPhPh138139140PdCl2141ClClLi2PdCl4CO, MeOHClAgBF4TMEDAPdLL142Cl+X-EEMePdClEEMeLL143PdLL+EEMe144EEMeMeEEEMeE145E = COOR146147148OOO+ArNCO5 mol% Pt(C2H
21、4)(PPh3)2toluene, reflux150NArArNOOPt+ArNOArNOPtO-CO2NArPt+ArNCO149Pd(0)OAc+LPdLLNu-PdNuLLNu152151153154PtCR1MeCOOMeLL1/4 (C3H5PtCl)4+2 L+TlOAcCH2Cl2- TlCl(3-allyl)PtLnOAc156R1MeC=C(OMe)(OTMS)157CH2Cl2- AcOSiMe3155WCpCpdilute HClNH4PF680%WCpCpPF6-+CH3LiEt2OWCpCpHMe159160158MoCpCpPF6-+161RNaBH4, THF7
22、0%MgClEt2O, 60%MoCpCpHHMoCpCpH162163RhICp*L80%RhCp*LBF4-+H-165166164RhCpi-Pr3PBF4-+167MeRhCp*LHHCH3LiTHF, -80oC71%RhCpi-Pr3P168AgBF4IrClCp*LIrCp*LBF4-+LiEt3BH170171169IrCp*OTf -+172IrCp*LHRTHF, -35oCto rt77%IrCp173AgBF4or MeLiOKPhPhOI2PhO174ZrClClCp*Cp*60%ZrCp*Cp*ZrCp*Cp*H176177175MgClC6H660-80oC85%
23、AgOTfCDCl3, 2 h-78oC to rt178Cp* = C5Me5MgClEt2O, reflux, 48 h, 91%5.8 5.8 丙炔醇碳酸酯的反应丙炔醇碳酸酯的反应 OCO2MeRROOMeOPdOMeRPdOMeRNuRNuNuHPd(O)Pd-CO2NuHNu -179180181OCO2MeOCO2MeOCO2MeCO2MeO+Pd2(dba)3dppe182183OOOCO2MeOCO2MeOPdOCO2MeOCO2Me+Pd2(dba)3.CHCl3dppeTHF, rt, 4 h+_H+CO2MeOOCO2MeOHOOCO2Me+- HCHO(25)XPdXPdRR+Pd(O)R - MOTHPHC4H9MeMeO2COTHPOC4H9MeOO+Pd(PPh3)4CuI, LiClOOOCO2MeR1OCO2MeR1R2R2CO2EtCO2EtOOOCO2EtR2OR1R2CO2EtorPd(dba)2, dppeEEEEEEEER1EEEER1( )Pd(0)( )n( )n+E = CO2Etn = 1, 2, 3n
