TRANSITION METAL -CATALYZED HOMOGENEOUS ASYMMETRIC HYDROGENATION - Catalytic Asymmetric Synthesis - page 364

TABLE 7.2. Asymmetric Hydrogenation of β , β - Disubstituted α - Dehydroamino Acids

R 1 COOMe R 1 COOMe

Chiral Rh catalysts
H 2

∗

R 2 NHAc R 2 NHAc

Ligand R 1 R 2 S / C Reaction Conditions a % ee (Confi g.) Reference

( S,S ) - Me -
DuPhos

Me Ph 500 Benzene, 25 ° C,

6 atm, 12 - 24 h

99.4 (2 S ,3 R ) 28b

( S,S,S,S ) - f -
KetalPhos

Me Me 100 THF, rt, 1 atm, 3 h 87.3 ( S ) 5 5

( R,R ) - ( S,S ) - Bu -
Trap

Me Me 100 i PrOH, 15 ° C, 1 atm 88 ( S ) 54b

( S,S ) - Cy - BisP * Me Me 500 MeOH, rt, 6 atm 90.9 ( R ) 35a

( S,S ) - t Bu -
MiniPhos

Me Me 500 MeOH, rt, 6 atm 87 ( R ) 5 6

( S,S ) - 43 Me Me 500 rt, 6 atm 87 ( S ) 5 7

( S,S ) - 42 Me Me 100 MeOH, rt, 20 atm 96.1 ( R ) 8 3

( R,R ) - Me - BPE Me Me 500 Benzene, 25 ° C,

6 atm, 12 - 24 h

98.2 ( R ) 28b

Et Et 500 Benzene, 25 ° C,

6 atm, 12 - 24 h

97.5 ( R ) 28b

Pr Pr 500 Benzene, 25 ° C,

6 atm, 12 - 24 h

96.8 ( R ) 28b

Me Et 500 Benzene, 25 ° C,

6 atm, 12 - 24 h

98.2 (2 R ,3 S ) 28b

Et Me 500 Benzene, 25 ° C,

6 atm, 12 - 24 h

98.3 (2 R ,3 R ) 28b

COOMe Me 500 Benzene, 25 ° C,

6 atm, 12 - 24 h

96.6 (2 R ,3 S ) 28b

a Complete conversion unless otherwise noted.

applications in any industrial process. A large number of catalytic systems, especially
Rh complexes of chiral diphosphine ligands, have been employed in the hydrogenation
of β-dehydroamino acid derivatives. For example, Rh complexes of BPE [122], DuPhos
[122,123] , BasPhos [124,125] , ButiPhane [126] , Cat AS ium M [29] , 44 [127] , 46 [127] ,
BICP [46] , t Bu - BisP * [128] , and 47 [129] as well as Ru complex of BINAP [86]
have all been reported to effectively catalyze the hydrogenation of ( E ) - ( β - acylamino)
acrylates with good enantioselectivities. Rh complexes of TangPhos [36b], DuanPhos
[37] , BINAPINE [130] , 40 [131] , 47 [129] , and 56 [95] are found to be equally or
more selective for ( Z ) - ( β-acylamino) acrylates. Although most of the studies were
carried out with relatively high catalyst loadings for screening purposes, an S/C ratio
of 10,000 was achieved by Rh-BINAPINE on a series of ( Z ) - 3 - aryl - 3 - (acylamino)acrylic
acid derivatives [130]. Some of the most selective results (>95% ee) are summarized in
Table 7.3 .