清华大学：《手性合成导论 Introduction to Chiral Synthesis》课程教学资源（PPT课件讲稿）第六章 不对称催化氢化及其它还原反应

2.碳碳双键的不对称催化氢化 2.1a-酰胺基丙烯酸不对称催化氢化 CO2H H2, Rh CO2H R NHAC Chiral ee% 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) S)-(R)-BPPFA 93(S (S, S)-SKEWPHOS 92(R S, S)-CYCPHOS 88(R (S, S)-Et-DuPHOS 99(S)

2. 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 R NHAc CO2 H H2 , Rh* R CO2 H * ---------------------------------------------------------- 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) (S)-(R)-BPPFA 93(S) (S,S)-SKEWPHOS 92(R) (S,S)-CYCPHOS 88(R) (S,S)-Et-DuPHOS 99(S) ----------------------------------------------------------

Ph2Po OPPH2 Ph2OP OPPh (R,R) (s,S)- CO,Me Rh-(S,S) CO,Me R NHCOMe 1 atm. rt NHAC R ee% Ph 95.7 4-CI-Ph 94.2 4-F-Ph 955 4-Br-Ph 96.3 4-MeO-Ph 962 4-Me-Ph 95.6 2-Furyl 97.2

Ph2 PO OPPH2 Ph2OP OPPh2 (R,R)- (S,S)- -------------------------------- R e.e% -------------------------------- Ph 95.7 4-Cl-Ph 94.2 4-F-Ph 95.5 4-Br-Ph 96.3 4-MeO-Ph 96.2 4-Me-Ph 95.6 2-Furyl 97.2 ------------------------------- R NHCOMe CO2Me Rh-(S,S)- 1 atm. rt. NHAc CO2Me

H PPh.o PPH COH Rh- SCO2H R R NHCOR NHAC R R ee% Me94.8 Me94.7 Ph 89.2 m-Br-Ph Me 93.5 O-CI-Ph Me 92.9

H OPPh2 H PPh2 O R NHCOR' CO2 H R NHAc Rh-* S CO2 H ------------------------------------ R R' e.e% ------------------------------------ H Me 94.8 Ph Me 94.7 Ph Ph 89.2 m-Br-Ph Me 93.5 o-Cl-Ph Me 92.9 -----------------------------------

NHPPh NHPPh2 NHPPh2 NHPPh2 NHPPh NHPPh2 NHPPh 2 NHPPh (R)-BDPAB (S)-BDPAB (R)-H8-BDPAB (S)-H8-BDPAB 1 atm. 5oC, 30min Me NHCOMe RNHCOMe quantitative ArH

NHPPh2 NHPPh2 NHPPh2 NHPPh2 NHPPh2 NHPPh2 NHPPh2 NHPPh2 (R)-BDPAB (S)-BDPAB (R)-H8-BDPAB (S)-H8-BDPAB R NHCOMe 1 atm. 5oC, 30min quantitative Ar M NHCOMe e H

2.2手性Rh-二茂铁基膦催化剂 H Me NR Fek-pphy NR2-NN NBu2 NEt2 PPh Me Rh CHMe2 Ar CO2H ArcO2ee%=958984(S) Ar=Ph, 4-CI-Ph, 4-MeO-Ph, 2-Naphthyl R Me Rh R、Me H n CO2H H2 Ph Ar\ coh R=Etee%=973(2s,3s)],Phee%=921(2s3R)

2.2 手性Rh-二茂铁基膦催化剂 PPh2 PPh2 N NR2 H Me Fe NR2 = N NBu2 NEt N 2 Ar Me CO2 H Me Rh-* H2 Ar CO2 H CHMe2 H Ar=Ph, 4-Cl-Ph, 4-MeO-Ph, 2-Naphthyl e.e%=95.8-98.4, (S) Ph R CO2 H Me Rh-* H2 Ar CO2 H H R Me H R=Et[e.e%=97.3(2s,3s)], Ph[e.e%=92.1(2S,3R)