2156
G. Hoge, B. Samas / Tetrahedron: Asymmetry 15 (2004) 2155–2157
Table 2. Asymmetric hydrogenation of methyl-3-acetamido-2-bute-
noate
OMs
R
OMs
H3B
CO2Me
NHAc
Catalyst 2 or 4
H3B
CO2Me
NHAc
6
H
P
P
P
H3B
H
20 psiH 2, THF
n-BuLi
R
R
5
8
7
(E) or (Z)
Entrya Catalyst
R
1. oxidative
coupling
Substrate isomer Time (min)
Eeb (%)
P
P
1
2
3
4
2
2
4
4
E
Z
E
Z
5
96 (R)
89 (R)
96 (S)
83 (S)
2. deboronation
45
15
75
R
(a)
1
a All reactions were performed at room temperature using 1 mol %
catalyst loading and 0.2 M substrate concentration.
b Ee of product was analyzed on a Chiral-DEX-CB GC column.
O
S
O
O
O
R
R
R
H2P
PH2
P
P
P
P
heat
10
n-BuLi
4. Recent reports have focused on catalysts that can
hydrogenate both (E)- and (Z)-isomers of this substrate
class with high enantioselectivity.6 Both catalysts 2 and
4 provided high ees (96%) for the hydrogenation of the
(E)-form of the substrate (entries 1 and 3). However,
while 4 produced 83% ee for the (Z)-form of the
substrate (entry 4), catalyst 2 produced an encouraging
89% (entry 3). In both cases, the (Z)-isomer was
hydrogenated several times more slowly than the
(E)-isomer.
R
R
(b)
9
11
3
Scheme 2. Synthesis of P-chirogenic bisphospholane ligands. (a) Eth-
ane backbone synthesis (R ¼ benzyl); (b) benzene backbone synthesis
(R ¼ benzyl).
Table 1 depicts the results of the asymmetric hydroge-
nation of a-acetamido dehydroamino acid derivatives
using both catalyst 2 and 4. Although enantiomeric
excesses using catalyst 2 ranged 77–95% (entries 1–4)
(methyl and phenyl substituted substrates), catalyst 4
displayed more consistency and better selectivity for
each entry (P95% ee). The enantiomeric excesses of
catalyst 4 are similar to those reported for Rh–Me–
DuPhos.4 In the case of entry 5, however, catalyst 2
provided better enantioselectivity (96%) than catalyst 4
(86%). b,b-Disubstituted a-acetamido dehydroamino
acid substrates are known to be among the most difficult
to hydrogenate with high enantioselectivity.5
3. Conclusion
Both catalysts 2 and 4 provide good enantioselectivity
for the catalyzed asymmetric hydrogenation of both the
a- and b-acetamido dehydroamino acid derivatives.
Although many other chiral phosphine ligand-metal
catalysts have a list of similar accomplishments, these
P-chirogenic ligands and their corresponding rhodium
catalysts are exemplary of a phosphine ligand class that
shows promise for diversifying the useful chiral ligand
and catalyst pool. Work is currently underway in our
laboratory in the exploration of novel P-chirogenic
bisphosphine ligands.
Table 1. Asymmetric hydrogenation of a-acetamido dehydroamino
acids
CO2R1
R3
AcHN
R2
CO2R1
R3
AcHN
R2
Catalyst 2 or 4
30 psiH 2, MeOH
R3
Acknowledgements
Entrya
R1
R2
Eeb (%)
catalyst 2
Eeb (%)
catalyst 4
Pfizer, Inc. is acknowledged for its continuing support
of this research.
1
2
3
4
5
Me
H
H
H
H
H
H
95 (R)
86 (R)
84 (R)
77 (R)
96 (R)
98 (S)
97 (S)
95 (S)
96 (S)
86 (S)
H
Me
H
Ph
Ph
Me
R2, R3 ¼ –C5H10
–
References and notes
a All reactions were performed at room temperature using 1 mol %
catalyst loading and 0.2 M substrate concentration. All reactions were
complete within 15 min.
1. A comprehensive reviewof chiral phosphorus ligands for
enantioselective hydrogenation has been published recently.
See: Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029–
3069.
b Ee of product was analyzed on a Chiral-
L-Val column.
2. Hoge, G. (submitted for publication).
Table 2 shows the results of the asymmetric hydroge-
nation of methyl 3-acetamido-2-butenoate, a b-acetam-
ido dehydroamino acid derivative, using catalysts 2 and
3. Hoge, G. J. Am. Chem. Soc. 2003, 125, 10219.
4. Burk, M. J.; Feaster, J. E.; Nugent, W. A.; Harlow, R. L. J.
Am. Chem. Soc. 1993, 115, 10125.
Hoge, Garrett
