第六章：氢化

1、第六章：不对称催化氢化及其它还原反应第六章：不对称催化氢化及其它还原反应 引言 碳碳双键的不对称催化氢化 羰基化合物的还原 亚胺的不对称还原 不对称氢转移反应 不对称氢化制备氟化合物1.1 氢化反应机理氢化反应机理H2H HCatWhy cat.is necessary?C CH HHOMOLUMO-1eHOMOLUMO1. 引言引言1960年以前年以前,非均相催化在催化领域里占主导地位非均相催化在催化领域里占主导地位.1965年年,Wilkinson发明了发明了Rh(PPh3)3Cl,温和条件氢化烯烃温和条件氢化烯烃. 1968年年,Honer和和Knowles独立报道了手性膦配体氢化独立报

2、道了手性膦配体氢化,e.e%=3-15%1971年年,Kagen发明了发明了Rh-DIOP, e.e%=80.引起反响引起反响.30年来年来,手性取代二膦在过渡有机金属催化反应中已经证明手性取代二膦在过渡有机金属催化反应中已经证明是最有用的多功能配体是最有用的多功能配体1.2 发展简史发展简史1.3 手性膦配体手性膦配体PPh2PPh2PPh2PPh2PPh2PPh2PROPHOS(S,S)-CHIRAPHOSCYCPHOSPPh2PPh2NPPh2PPh2RPPh2PPh2(+)-DIPMCDEGPHOS(R,R)-DPCPOOPPh2PPh2DIOPPPh2PPh2NORPHOSPPh2P

3、Ph2(-)-MENOPPh2PPh2PPOMeMeO(R)-BINAP(R,R)-DIPAMP2. 碳碳双键的不对称催化氢化碳碳双键的不对称催化氢化2.1 -酰胺基丙烯酸不对称催化氢化酰胺基丙烯酸不对称催化氢化NHAcRCO2HH2, Rh*RCO2H*-Chiral e.e% ligands R=Ph R=H-(R,R)-DIPAMP 96(S) 94(S)(S,S)-CHIRAPHOS 99(R) 91(R)(S,S)-NORPHOS 95(S) 90(R)(R,R)-DIOP 85(R) 73(R)(S,S)BPPM 91(R) 98.5(R)(S)-BINAP 100(R) 98(R

4、)(S)-(R)-BPPFA 93(S) (S,S)-SKEWPHOS 92(R)(S,S)-CYCPHOS 88(R)(S,S)-Et-DuPHOS 99(S)-Ph2POOPPH2OPPh2Ph2OP(R,R)-(S,S)-R e.e%-Ph 95.74-Cl-Ph 94.24-F-Ph 95.54-Br-Ph 96.34-MeO-Ph 96.24-Me-Ph 95.62-Furyl 97.2-NHCOMeRCO2MeRh-(S,S)-1 atm. rt.NHAcCO2MeHOPPh2HPPh2ONHCORRCO2HRNHAcCO2HRh-*S-R R e.e%-H Me 94.8Ph M

5、e 94.7Ph Ph 89.2m-Br-Ph Me 93.5o-Cl-Ph Me 92.9- NHPPh2NHPPh2NHPPh2NHPPh2NHPPh2NHPPh2NHPPh2NHPPh2(R)-BDPAB(S)-BDPAB(R)-H8-BDPAB(S)-H8-BDPABRNHCOMe1 atm. 5oC, 30minquantitativeArNHCOMeMeH2.2 手性手性Rh-二茂铁基膦催化剂二茂铁基膦催化剂PPh2PPh2NNR2H MeFeNR2= NNBu2NEt2NArMeCO2HMeRh-*H2ArCO2HCHMe2HAr=Ph, 4-Cl-Ph, 4-MeO-Ph, 2

6、-Naphthyle.e%=95.8-98.4, (S)PhRCO2HMeRh-*H2ArCO2HHRMeHR=Ete.e%=97.3(2s,3s), Phe.e%=92.1(2S,3R)2.3 钴络合物催化的钴络合物催化的 , -不饱和酯氢化反应不饱和酯氢化反应NHNRRCNR=CH2OSiMe2Bu- CH2OEt CMe2OHRCO2EtNaBH4, 1mol%CoCl2,1.2mol% Cat 1, 25oCRCO2Et*-E/Z R Y% e.e% R/S/+/-E PhCH2CH2 97 94 (R)-(+)Z Me2C=CHCH2CH2 95 94 (S)-(-)E PhCH2C

7、H2 95 94 (R)-(+)Z Me2C=CHCH2CH2 94 94 (S)-(-)E Me2CH 84 96 (S)-(-)Z Me2CH 86 90 (R)-(+)E Ph 95 81 (S)-(+)Z Ph 97 73 (R)-(-)-2.4. 一些有用的实例一些有用的实例PPAr2Ar2RuOOOOMeMeRu-(R)-BINAPOHRu-(S)-BINAP30atm.H2,MeOH,20oCMeOHRu-(R)-BINAP100%Y,96-99%e.eVatamine EOHRu-(S)-BINAP30atm.H2,MeOH,20oCMeOHNAcMeOMeOOMeOMeRu-

8、(R)-BINAP,EtOH,CH2Cl2,23oC4atm. H2, quantitativeNAcMeOMeOOMeOMe99.5%e.eCO2HMeORu-(S)-BINAP, 135atm. H2S/C=215CO2HMeO(S)-NaproxonY%=92, e.e 97%OHRu-(R)-BINAPOHRRRSIDE CHAIN OF VATAMINE K AND E3. 羰基化合物的还原3.1 BINAl-H还原OOAlHOROOAlHOR(S)-BINAL-H(R)-BINAL-HLiLiRRO(S)-(R)-RROHHRRHHO-Ketone BINAL-H Y% e.e%

9、R/S-C6H5COCH3 R 61 95 RC6H5COC2H5 S 62 98 SC6H5CO-n-C3H7 S 78 100 SC6H5CO-n-C4H9 S 64 100 SC6H5COCHMe2 S 68 71 SC6H5COCMe3 R 80 44 Ra-Tetralone R 91 62 R-RROR-S-RROHHRRHHORROR-RROHHS-RRHHOOHHCO2MeCO2MeOHHOHOHOORCO2MeHOHTHPOTHPO3.2 催化氢化ROEtOONH2BINAP-Ru-Br2H2ROEtONH2OHROEtONH2OH+-R Br2-Ru-BINAP Y% Ra

10、tio e.e%-PhCH2 R 97 99:1 99(CH3)2CHCH2 S 96 9:91 99(CH3)2CHCH2 R 99 99:1 97Cyclohexylmethyl R 92 99:1 100-OORu-(R)-BINAPor Ru-(S)-BINAPOHOHOHOHOR(R,R)-(S,S)-Y%95, e.e%99.9OMeOORu-(R)-BINAPOMeOHO100atm. 19-30oCMeOH-Cat. System S/C h Y% e.e%-Ru(OCOCH3)2(BINAP) 1400 60 1 -Ru(OCOCH3)2(BINAP)+2F3CCO2H 16

11、20 32 99 15Ru(OCOCH3)2(BINAP)+2HClO4 1620 32 99 51Ru(OCOCH3)2(BINAP)+2HCl 1800 32 99 51Ru(OCOCH3)2(BINAP)+2HCl 10000 64 98 96RuCl2(BINAP) 2000 36 99 99RuBr2(BINAP) 2100 40 99 99RuI2(BINAP) 1400 40 99 99-RuClClPPNN*Rapid, high yield, clean, mild, effctiveWith the highst activity of homo-cat ever repi

12、rted.OH2OHY%=100, e.e%=943.3 硼杂恶唑烷体系 Chemzyme,CBS体系(Corey-Bakshi-Shibata)2R1R2C=O + BH3R=CH3,Cat.THF, 25oC, 1min(R1R2CHO-)2BHR1R2CHOH-Ketone BH3eq. Cat.e.q R=CH3 R/S/e.e%-C6H5COCH3 2.0 1 R/97C6H5COCH3 1.0 0.1 R/97C6H5COCH3 1.2 0.025 R/95C6H5COC2H5 1.2 0.05 R/86C6H5COC2H5 1.0 0.05 R/88C6H5COC2H5 0.6

13、0.05 R/90t-BuCOCH3 0.6 0.05 R/88t-BuCOCH3 0.6 0.1 R/92a-tetralone 0.6 0.05 R/89C6H5COCH2Cl 0.6 0.05 S/97-NBOHPhPhRR=H, Me, BuClO0.6eqBH3Cat,R=MeClHOHNaI97%-99%IHOHCH3NH299%NHOHH1.NaH2.p-F3CC6H4Cl3.HCl94%-96%NHOH2 ClCF3(R-)-福西丁4. 亚胺的不对称还原NPh2PPPh2CO2Bu-t(2S,4S)-BPPMONMe(2S,4S)-BPPM-IrBH3ONMeS6 StepsO

14、NMeOCO2HFNNMe左氟沙星：杀菌剂对革兰氏阳性菌和阴性菌都有强力杀菌活性TiFFSNRnPhSiH3,H2NRnRRNRRRNR橙黄色固体,活性极高,对空气稳定,低氢气压和高氢气压都有高的选择性CH3NCH3CAT eq. 1/5000e.e%=97N-R大了不好CH3NBn96h后,55%转化,47%e.eTiFFNBnPhSiH3piperidine/MeOH60oC1.5-4eq H2NRCH3NBnH*2h完成, 97%Y,98%e.e 伯胺有显著的催化作用5. 不对称氢转移反应NRuNTsTsRNRuNTsTsR(R,R)-(S,S)ONHCbzNHCbzOHNHCbzOH(

15、R,R)-(S,S)-SmNOOBnPhPhNPPh2PPh2NPPh2PPh2M H6. 不对称氢化制备氟化合物HHCF3O2CCH3H3CCF3RRRu(COD)L*X-H2,MeOHPPMeOOMe(R,R)-DIPAMPH2(3.5atm)X=BF4 77%e.eR=H, R=OAcPPMe-DuPHOSH2(2atm)X-=OTf, 94%e.eR=H, R=OAcPPC2H5C2H5C2H5C2H5H2(2atm), 95e.eR=OAc, R=OAcPPh2PPh2(R)-BINAP-Ru(II)A=Ru2Cl4(R)BINAP2NEt3B=RuOCOCMe32(R)BINAP2RFCO2H(R)-BINAP-Ru(II), 1%molRCO2HFA R=C3H7, 91%e.