Selective catalytic hydrogenation of γ-amino α,β-unsaturated esters in the presence of hydrogenable protecting groups

Article abstract of DOI:10.1055/s-1999-3471

The chemoselective catalytic hydrogenation of substituted γ-amino α,β-unsaturated esters bearing benzyl ether, benzyl ester functionalities and N-Cbz protecting groups by 3% Pd/C in EtOAc was investigated. The results revealed a good selectivity for subst

Full text of DOI:10.1055/s-1999-3471

PAPER
873
Selective Catalytic Hydrogenation of g-Amino a,b-Unsaturated Esters in the
Presence of Hydrogenable Protecting Groups
Domenico Misiti,a Giovanni Zappia,* a Giuliano Delle Monacheb
a Dip. di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Università “La Sapienza”, P.le A. Moro 5, 00185 Roma, Italy
b Centro Chimica dei Recettori, Università Cattolica del Sacro Cuore, Largo F. Vito 1, I-00168 Roma, Italy
Fax +39(6)49912780; E-mail: g.zappia@caspur.it
Received 3 August 1998; revised 2 October 1998
tion/Wittig-Horner reaction from the N-protected a-ami-
Abstract: The chemoselective catalytic hydrogenation of substitut-
no
acid
esters
with
the
proper
lithium
ed g-amino a,b-unsaturated esters bearing benzyl ether, benzyl ester
functionalities and N-Cbz protecting groups by 3% Pd/C in EtOAc
was investigated. The results revealed a good selectivity for sub-
strates with benzyl ethers and benzyl esters in the side chain and for
a,b-unsaturated benzyl esters. Moderate selectivity was observed
for substrates with N-Cbz protecting group.
trialkylphosphonoacetate according to Knaus et al.9
Key words: chemoselective hydrogenation, 3% Pd/C, g-amino a,b-
unsaturated esters, protected g-amino acids
g-Amino acids possess various biological activities, espe-
cially as enzyme inhibitors; for instance g-aminoadipic
acid is able to bind the Glu and Asp receptors,1 whilst 4-
amino-5-hydroxypentanoic acid is an inhibitor of en-
zymes involved in the neurotransmission mechanism.2
Few general methods are described in literature3 to obtain
enantiomerically pure g-amino acids, most of them start-
ing from a-amino acids. A simple synthetic strategy to
prepare these compounds is based on a Wittig homologa-
tion of a suitable a-amino aldehyde, followed by reduc-
tion to the saturated ester. Although a number of methods4
are available for the reduction of a,b-unsaturated esters,
the hydrogenation with heterogeneous catalyst is the
method which combines mild conditions with high yields.
However, this synthetic approach seems to be precluded
by the presence of other reducible functionalities, e.g. by
the presence of protecting groups labile under hydrogena-
tion conditions. While several catalytic systems are avail-
able for the hydrogenation of alkenes, selective reduction
in the presence of other hydrogenable groups has not been
fully addressed. During the course of synthetic studies,5
we searched for a method to hydrogenate some substituted
g-amino a,b-unsaturated esters in the presence of benzyl
ether, benzyl ester functionalities and N-benzyloxycarbo-
nyl protecting groups. A review of the literature revealed
that only few examples of selective reduction of alkenes
in the presence of a benzyl ether are reported. These meth-
Scheme
Each substrate was treated under the same conditions;
namely it was dissolved in freshly dried10 EtOAc (0.2 M)
containing a catalytic amount (5% by wt) of commercial
3% Pd/C. The reaction mixture was stirred under an atmo-
spheric pressure of H2 until TLC11 indicated the disap-
pearance of the g-amino a,b-unsaturated ester. Reactions
were complete usually within 1 hour, but some experi-
ments were allowed to stand for 16 hours to evaluate the
selectivity by time.
The results, summarized in the Table, indicate that under
the above reaction conditions a,b-unsaturated esters can
be selectively reduced in the presence of benzyl ether,
benzyl ester functionalities and, in a less selective way,
also in the presence of N-benzyloxycarbonyl protecting
group.
Initially, experiments were run with g-amino a,b-unsatur-
ated esters possessing a benzyl ether in the side chain 1a-
c; clean reduction occurred within 1 hour and the saturat-
ed esters 2a-c were obtained in high yields (~ 95%) with-
out any effect on the ether function.
When the reaction was allowed to stand for 16 hours (en-
try 1a) the reduction product 2a was obtained in 90%
yield, confirming the good selectivity towards the benzyl
ether protecting group. A control of the optical purity12 for
2a gave an ee value of 95%. Good yields (90-93%) were
also obtained for the catalytic reduction of g-amino a,b-
unsaturated esters carrying a benzyl ester in the side chain
(compounds 1d, 1e); moreover the selectivity was con-
firmed when the compound 1d was allowed to stand for
16 hours and the saturated product 2d was obtained in
82% yield. Notably, a,b-unsaturated benzyl esters 1f and
6
ods involve the use of 5% Rh/Al2O3 or 5% Pd/C in the
presence of 5% butylamine or ammonia,7 as well as the
Lindlar catalyst in MeOH.8
We wish to report here the results obtained by the use of
3% Pd/C in EtOAc for the selective catalytic hydrogena-
tion of substituted g-amino a,b-unsaturated esters in the
presence of the above hydrogenable protecting groups
(Scheme). All the starting trans-a,b-unsaturated esters
were synthesized in 60-70% yields by a one-pot reduc-
Synthesis 1999, No. 5, 873–877 ISSN 0039-7881 © Thieme Stuttgart · New York

874
D. Misiti et al.
PAPER
Table Selective Reduction of Substituted g-Amino a,b-Unsaturated Esters in the Presence of Benzyl Ether, Benzyl Ester and N-Cbz
Functionalities.
Entry
Substrate 1
Product 2
Time
Yield (%)
a
50 min
16 h
94
90
b
c
1 h
1 h
96
95
d
e
1 h
16 h
90
82
1 h
93
f
1 h
16 h
95
83
g
h
i
1 h
92
45 min
3 h
60
<10
40 min
40 min
62
60
j
k
l
45 min
40 min
45 min
64
72
76
m
Synthesis 1999, No. 5, 873–877 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Hydrogenation of g-Amino a,b-Unsaturated Esters in the Presence of Hydrogenable Protecting Groups
875
with an equal amount of EtOAc and filtered through a paid of
Celite. The solvent was removed under reduced pressure and the
residue was passed through a short silica gel column (50% EtOAc/
hexane) to give the corresponding hydrogenated compound.
1g were also selectively reduced in 92 and 95% yield, re-
spectively, without any modification of the benzyl ester
function. The reaction conditions were again so mild to in-
hibit the hydrogenolysis of the benzyl ester in 1f even if
the reaction was allowed for 16 hours, and the saturated
compound 2f was obtained in 83% yield. To our knowl-
edge, this is the first example of selective catalytic hydro-
genation under heterogeneous conditions of a,b-
unsaturated benzyl esters to the saturated compounds. A
control of the enantiomeric excess for the compound 2g12
gave a value of 96%. By contrast the selectivity was mod-
erate when a benzyloxycarbonyl group was present as
protecting group for an amine function (compounds 1h-
k).
(R)-Methyl 5-Benzyloxy 4-[(tert-butoxycarbonyl)amino]pen-
tanoate (2a)
mp 45-46°C; [a]D +19.98 (c = 2.12, CHCl3)
1H NMR: d = 7.40-7.25 (5 H, m, C6H5), 4.77 (1 H, br d , J = 9.0 Hz,
NH), 4.53, 4.49 (1 H each, d, J = 12.0 Hz, OCH2C6H5), 3.78 (1 H,
m, S J = 31.0 Hz, CHN), 3.67 (3 H, s, OCH3), 3.47 (2 H, d, J = 4.0
Hz, CH2O), 2.38 (2 H, t, J = 7.5 Hz, CH2CO), 1.94 (1 H, dtd, J =
14.0, 7.5, 5.5 Hz, CHAHB), 1.86 (1 H, dq, J = 14.0, 7.5 Hz, CHAHB),
1.43 (9 H, s, 3 CH3).
13C NMR: d = 173.89 (s, COO), 155.59 (s, CON), 138.03, 128.39,
127.69, 127.58 (s, 2 d, d, 2 d, C6H5), 79.28 (s, quat C), 73.20 (t,
OCH2C6H5), 72.11 (t, CH2O), 51.61 (q, OCH3), 49.91 (d, CHN),
30.81 (t, CH2CO), 28.36 (q, 3 CH3), 27.55 (t, CH2).
Within the time required for the reduction of the a,b-un-
saturated esters the saturated products were obtained in
yields ranging from 60-64%. The byproduct was the cor-
responding 2-pyrrolidinone, formed by the loss of the Cbz
group and cyclization. The stability of Cbz under these
conditions was time dependent as shown by the substrate
1h where the Cbz was almost entirely removed within 3
hours.
(R,S)-Methyl 5-Benzyloxy-4-[(fluorenylmethoxycarbonyl)ami-
no]pentanoate (2b)
mp 99-100 °C
1H NMR: d = 7.76 (2 H, br d, J = 7.5 Hz, Fmoc), 7.59 (2 H, br d, J
= 7.5 Hz, Fmoc), 7.40 (2 H, br t, J = 7.5Hz, Fmoc), 7.35-7.25 (5 H,
m, C6H5), 7.31 (2H, br t, J = 7.5 Hz, Fmoc), 5.07 (1 H, br d, J = 9.0
Hz, NH), 4.53, 4.49 (1 H each, d, J = 12.0 Hz, OCH2C6H5), 4.42 (2
H, d, J = 7.0 Hz, CH2), 4.21 (1 H, t, J = 7.0 Hz, CH), 3.85 (1 H, m,
S J = 32 Hz, CHN), 3.66 (3H, s, OCH3), 3.49 (2H, d, J = 4.0 Hz,
CH2O), 2.38 (2H, t, J = 7.5 Hz, CH2CO), 1.96, 1.89 (1H each, dq, J
= 14.0, 7.5 Hz, CH2).
Additional studies were performed on substrates with two
or three hydrogenable protecting groups. The substrate 1l
was thus reduced in 72% yield to the saturated product 2l,
whereas the compound 1m, carrying all the protecting
groups studied up to now, was hydrogenated in 30 min-
utes in 76% yield. These results, together with those ob-
tained for 1h-k, indicate that, in the case of g-amino a,b-
unsaturated esters carrying a N-Cbz protecting group, the
yields of saturated products are variable and substrate de-
pending.
13C NMR: d = 173.78 (s, COO), 156.10 (s, CON), 143.93, 143.89,
141,29 (s, s, 2 s, Fmoc), 137.89, 128.42, 127.75, 127.64 (s, 2 d, d, 2
d, C6H5), 127.01, 125.02, 119.83, 103.32 (d each, Fmoc), 73.25 (t,
OCH2C6H5), 71.82 (t, CH2O), 66.59 (t, CO2CH2), 51.62 (q, OCH3),
50.61 (d, CHN), 47.28 (d, CH), 30.72 (t, CH2CO), 27.31 (t, CH2).
(R)-Methyl 5-Benzyloxy-4-[(ethoxycarbonyl)amino]pen-
tanoate (2c)
oil; [a]D +10.5 (c = 2.2, CHCl3)
In summary we have shown that the combination of cata- 1H NMR: d = 7.40-7.25 (5 H, m, C6H5), 4.94 (1 H, br d , J = 8.5 Hz,
NH), 4.53, 4.49 (1 H each, d, J = 12.0 Hz, OCH2C6H5), 4.09 (2 H,
q, J = 7.0 Hz, OCH2CH3), 3.83 (1 H, m, S J = 31.0 Hz, CHN), 3.49
lytic amount (5% by wt) of commercial 3% Pd/C in
EtOAc is the system of choice for the selective hydroge-
(2 H, d, J = 4.0 Hz, CH2O), 2.39 (2 H, t, J = 7.5 Hz, CH2CO), 1.94
nation of substituted g-amino a,b-unsaturated esters when
(1 H, dtd, J = 14.0, 7.5, 5.5 Hz, CHAHB), 1.86 (1 H, dq, J = 14.0, 7.5
a benzyl ether or benzyl ester functionality is present in
the molecule. A lower selectivity was instead observed
when a N-benzyloxycarbonyl group was present. Follow-
ing the above results, we believe that the present method
Hz, CHAHB), 1.23 (3 H, t, J = 7.0 Hz, CH3).
13C NMR: d =173.83 (s, COO), 156.34 (s, CON), 137.83, 128.39,
127.71, 127.58 (s, 2 d, d, 2 d, C6H5), 73.23 (t, OCH2C6H5), 71.95 (t,
CH2O), 60.78 (t, OCH2CH3), 51.62 (q, OCH3), 50.38 (d, CHN),
30.74 (t, CH2CO), 27.45 (t, CH2), 14.57 (q, CH3).
should find broad application in organic synthesis.
(R)-Methyl 4-[(Fluorenylmethoxycarbonyl)amino]-6-benzylox-
ycarbonylhexanoate (2d)
Melting points were determined in open capillaries using a Büchi
apparatus and are uncorrected. 1H and 13C NMR spectra were run on
a Varian Gemini 300 spectrometer at 300 and 75 MHz, respectively,
in CDCl3. Chemical shifts (d scale) are relative to TMS as internal
reference. The 1H and 13C NMR data of compound 2j were collected
at T = 60 °C, since at r.t. double signals, due to the restricted rotation
of the N-CO bond, were observed. Optical rotations were deter-
mined on a Perkin Elmer 243 polarimeter at 23 °C (concentration g/
100 mL). TLC was performed on Merck silica gel 60 F254 glass
plates. Compounds 2a-m gave C, H, N analysis ±0.3%.
mp 123-124 °C; [a]D +11.9 (c = 0.53, CHCl3)
1H NMR: d = 7.74 (2 H, br d , J = 7.5 Hz, Fmoc), 7.56 (2 H, br d, J
= 7.5 Hz, Fmoc), 7.38 (2 H, br t, J = 7.5 Hz, Fmoc), 7.33 (5 H, br s,
C6H5), 7.29 (2 H, br t, J = 7.5 Hz, Fmoc), 5.09 (2 H, s, OCH2), 4.61
(1 H, d, J = 9.0 Hz, NH), 4.40 (2 H, d, J = 6.5 Hz, CH2, Fmoc), 4.17
(1 H, t, J = 6.5 Hz, CH, Fmoc), 3.66 (1 H, m, S J = 37.0 Hz, CHN),
3.64 (3 H, s, OCH3), 2.40, 2.34 (2 H each, br t, J = 7.5 Hz, 2
CH2CO), 1.88, 1.86, 1.74, 1.68 (1 H each, m, 2 CH2).
13C NMR: d =173.80 (s, COO), 156.16 (s, CON), 143.87, 141.34 (s
each, Fmoc), 135.93, 128.57, 128.26 (s, 2 d, 3 d, C6H5), 127.69,
127.06, 124.99, 119.96 (d each, Fmoc), 66.43 (t, OCH2), 51.72 (q,
OCH3), 50.87 (d, CHN), 47.36 (d, CH, Fmoc), 30.91, 30.66 (t each,
2 CH2CO), 30.49, 29.71 (t each, 2 CH2).
Selective Catalytic Hydrogenation of g-Amino a,b-Unsaturated
Esters; General Procedure
A mixture of the appropriate a,b-unsaturated ester (1 mmol), 3%
Pd/C (5% by weight, Aldrich) in freshly distilled EtOAc (5 mL) was
subjected to two N2/H2 cycles and then stirred under a H2 filled bal-
lon. After the proper time (Table) the reaction mixture was diluted
Synthesis 1999, No. 5, 873–877 ISSN 0039-7881 © Thieme Stuttgart · New York

876
D. Misiti et al.
PAPER
(R)-Methyl 4-[tert-Butoxycarbonyl)amino]-6-benzyloxycarbo-
nylhexanoate (2e)
(S)-1-(Benzyloxycarbonyl)-2-(2-methoxycarbonyl)ethyl pyrro-
lidine (2j)
mp 38-39 °C; [a]D -4.06 (c = 2.44, CHCl3)
oil; [a]D -37.8 (c = 1.83, CHCl3)
1H NMR: d = 7.36 (5 H, br s, C6H5), 5.12 (2 H, s, OCH2), 4.31 (1 H,
d, J = 9.5 Hz, NH), 3.67 (3 H, s, OCH3), 3.60 (1 H, dp, J = 9.5,
4.5Hz, CHN), 2.44, 2.38 (2 H each, t, J = 7.5 Hz, 2 CH2CO), 1.87,
1.85 (1 H each, dtd, J = 14.0, 7.5, 4.5 Hz, CH2), 1.78, 1.76 (1 H each,
m, CH2), 1.42 (9 H, s, 3 CH3).
1H NMR (60 °C): d = 7.40-7.25 (5 H, m, C6H5), 5.12 (2 H, s,
OCH2), 3.91 (1 H, m, SJ = 23.5 Hz, CHN), 3.62 (3 H, s, OCH3),
3.47 (1 H, br dt, J = 11.0, 7.5 Hz, CHACHBN), 3.36 (1 H, ddd, J =
11.0, 7.0, 5.0 Hz, CHACHBN), 2.32 (2 H, t, J = 7.5 Hz, CH2CO),
1.96, 1.68 (1 H each, m, CH2), 1.88, 1.62 (1 H each, m, CH2), 1.83
(1 H, ddd, J = 14.0 Hz, CHCHD), 1.74 (1 H, ddd, J = 14.0, 7.5, 6.0
Hz, CHCHD).
13C NMR (60 °C): d = 173.42 (s, COO), 155.03 (s, CON), 137.06,
128.31, 127.75, 127.72 (s, 2 d, d, 2 d, C6H5), 66.61, (t, OCH2), 56.95
(br d, CHN), 51.24 (q, OCH3), 30.92 (t, CH2CO), 30.38 (br t, CH2),
29.69 (t, CH2), 23.36 (br t, CH2).
13C NMR: d =173.87, 173.18 (s each, 2 COO), 155.67 (s, CON),
135.93, 128.59, 128.25 (s, 2 d, 3 d, C6H5), 79.33 (s, quat C), 66.39
(t, OCH2), 51.71 (q, OCH3), 50.11 (d, CHN), 31.00, 30.73 (t, 3 t, 2
CH2CO, 2 CH2), 28.38 (q, 3 CH3).
(R)-Benzyl 6-Methyl-4-[(tert-butoxycarbonyl)amino]hep-
tanoate (2f)
mp 71-72 °C; [a]D -7.13 (c = 2, CHCl3)
(R)-Methyl 4-[(Benzyloxycarbonyl)amino]-5-tert-butoxycarbo-
nylpentanoate (2k)
1H NMR: d = 7.35 (5 H, s, C6H5), 5.12 (2 H, s, OCH2), 4.31 (1 H, br
d , J = 9.0 Hz, NH), 3.68 (1 H, m, S J = 37.0 Hz, CHN), 2.44 (2 H,
br t, J = 7.5 Hz, CH2CO), 1.85 (1 H, dq, J = 13.0, 7.5 CHAHBCO),
1.67 (1 H, m, CHAHBCH2CO), 1.59 (1 H, m, CH), 0.91, 0.90 (3 H
each, d, J = 6.5 Hz, 2 CH3).
mp 55-56 °C; [a]D 15.21 (c = 2.11, CHCl3).
1H NMR: d = 7.35 (5 H, m, OCH2C6H5), 5.08 (2 H, s, OCH2), 3.98
(1 H, dtt, J = 9.5, 7.5, 5.5 Hz, CHN), 3.65 (3 H, s, OCH3), 2.50, 2.43
(1 H each, dd, J = 16.0, 5.5 Hz, CH2CO), 2.40 (2 H, t, J = 7.5 Hz,
CH2COOCH3), 1.43 (9 H, s, 3 CH3).
13C NMR: d = 173.47 (s, COO), 155.61 (s, CON), 135.96, 128.52,
128.19 (s, 2 d, 3 d, C6H5), 79.40 (s, quat C), 66.27 (t, OCH2), 48.42
(d, CHN), 45.12 (t, CH2CH), 31.11, 30.97 (t each, CH2CO, CH2),
28.36 (q, 3 CH3), 24.92, 23.01 (q each, 2 CH3), 22.21 (d, CH).
13C NMR: d = 173.61 (s, CO2CH3), 170.56 (s, CO2C4H9-t), 155.87
(s, CON), 136.51, 128.48, 128.05, 128.02 (s, 2 d, 2 d, d, C6H5),
81.27 (s, quat C), 66.65 (t, OCH2), 51.66 (q, OCH3), 48.01 (d,
CHN), 40.37 (t, CH2CO), 30.84 (t, CH2CO), 29.55 (t, CH2), 28.04
(q, 3 CH3).
(R)-Benzyl 5-Phenyl-4-[(tert-butoxycarbonyl)amino]pen-
tanoate (2g)
mp 93-94 °C; [a]D +7.58 (c = 2.42, CHCl3)
(R)-Methyl 5-Benzyloxy-4-[(benzyloxycarbonyl)amino]pen-
tanoate (2l)
1H NMR: d = 7.34 (5 H, br s, OCH2C6H5), 7.27, 7.21, 7.16 (2 H d,
1 H t, 2 H br d, J = 8.0 Hz, CH2C6H5), 5.10 (2 H, s, OCH2), 4.37 (1
H, d, J = 9.0 Hz, NH), 3.84 (1 H, m, S J = 37.0 Hz, CHN), 2.81, 2.74
(1 H each, dd, J = 13.0, 7.0 Hz, CH2C6H5), 2.46 (1 H, ddd, J = 16.0,
9.0, 7.0 Hz, CHAHBCO), 2.40 (1 H, dt, J = 16.0, 7.5 Hz, CHAHB-
CO), 1.88 (1 H, dddd, J = 14.0, 9.0, 7.0, 4.0 Hz, CHCHD), 1.62 (1 H,
ddt, J = 14.0, 10.5, 7.5 Hz CHCHD), 1.39 (9 H, s, 3 CH3).
mp 53-54 °C; [a]D +16.25 (c = 3.95, CHCl3)
1H NMR: d = 7.45-7.30 (5 H, m, CO2CH2C6H5), 7.41 (5 H, br s,
C6H5), 5.16 (2 H, s, CO2CH2), 5.12 (1 H, br d , J = 9.0 Hz, NH),
4.58, 4.54 (1 H each, d, J = 12.0 Hz, OCH2), 3.92 (1 H, m, SJ = 31.0
Hz, CHN), 3.71 (3 H, s, OCH3), 3.55 (2 H, d, J = 4.0 Hz, CH2O),
2.45 (2 H, t, J = 7.5 Hz, CH2CO), 2.01, 1.93 (1 H each, dq, J = 14.0,
7.0 Hz, CH2).
13C NMR: d = 173.29 (s, COO), 155.46 (s, CON), 137.79, 129.43,
128.40, 126.42 (s, 2 d, 2 d, d, CH2C6H5), 135.90, 128.55, 128.20 (s,
2 d, 3 d, OCH2C6H5), 79.22 (s, quat C), 66.33 (t, OCH2), 51.38 (d,
CHN), 41.75 (t, CH2C6H5), 31.17 (t, CH2CO), 29.29 (t, CH2), 28.35
(q, 3 CH3).
13C NMR: d = 173.76 (s, COO), 156.07 (s, CON), 137.88, 128.39,
127.71, 127.57 (s, 2 d, d, 2 d, CH2OCH2C6H5), 136.49, 128.48,
128.05, 128.02 (s, 2 d, 2 d, d, C6H5), 73.23 (t, CH2OCH2C6H5),
71.82 (t, CH2OCH2C6H5), 66.67 (t, OCH2), 51.60 (q, OCH3), 50.58
(d, CHN), 30.71 (t, CH2CO), 27.41 (t, CH2).
(R,S)-Methyl 5-Phenyl-4-[(benzyloxycarbonyl)amino]pen-
tanoate (2h):
(R)-Benzyl 5-benzyloxy-4-[(benzyloxycarbonyl)amino]pen-
tanoate (2m)
mp 61-62 °C
1H NMR: d = 7.30-7.14 (5 H, m, OCH2C6H5), 7.26, 7.24, 7.16 (2 H
d, 1 H t, 2 H br d, J = 7.5 Hz, C6H5), 5.07 (2 H, s, OCH2), 4.65 (1 H,
d, J = 9.0 Hz, NH), 3.91 (1 H, m, S J = 36.0Hz, CHN), 3.62 (3 H, s,
OCH3), 2.85, 2.76 (1 H each, dd, J = 14.0, 7.0 Hz, CH2C6H5), 2.37
(2 H, t, J = 7.5 Hz, CH2CO), 1.88 (1 H, dtd, J = 14.0, 7.5, 4.0 Hz,
CHAHB), 1.65 (1H, dq, J = 14.0, 7.5 Hz, CHAHB).
mp 69-70 °C; [a]D +17.76 (c =1.69, CHCl3)
1H NMR: d = 7.36-7.23 (5 H, m, CH2OCH2C6H5), 7.33 (10 H, br s,
2 C6H5), 5.09, 5.07 (2 H each, s, 2 CO2CH2), 5.06 (1 H, br d , J = 9.0
Hz, NH), 4.50, 4.46 (1 H each, d, J = 12.0 Hz, OCH2), 3.86 (1 H,
dtt, J = 9.0, 7.0, 4.0 Hz, CHN), 3.48 (1 H, d, J = 4.0 Hz, CH2O), 2.43
(2 H, t, J = 7.5 Hz, CH2CO), 1.97, 1.87 (1 H each, dq, J = 14.0, 7.0
Hz, CH2).
13C NMR: d = 173.91 (s, COO), 155.94 (s, CON), 137.46, 129.40,
128.48, 126.55 (s, 2 d, 2 d, d, CH2C6H5), 135.92, 128.48, 128.06,
127.96 (s, 2 d, d, 2 d, C6H5), 66.56 (t, OCH2), 52.11 (d, CHN), 51.67
(q, OCH3), 41.59 (t, CH2C6H5), 30.87 (t, CH2CO), 29.21 (t, CH2).
13C NMR: d = 173.11 (s, COO), 156.05 (s, CON), 137.87, 136.46,
128.48, 128.49, 127.71, 127.57 (s, s, 2 d, 2 d, 2 d, 4 d, 2
CO2CH2C6H5), 135.90, 128.51, 128.05, 128.02 (s, 2 d, 2 d, d, C6H5),
73.20 (t, CH2OCH2C6H5), 71.82 (t, CH2OCH2C6H5), 66.67, 66.29 (t
each, 2 OCH2), 50.53 (d, CHN), 30.94 (t, CH2CO), 27.36 (t, CH2).
(S)-Methyl 4[(Benzyloxycarbonyl)amino]pentanoate (2i):
mp 47-48 °C; [a]D +8.44 (c = 1.95, CHCl3)
1H NMR: d = 7.40-7.25 (5 H, m, C6H5), 5.08 (2 H, s, OCH2), 4.65
(1 H, d, J = 8.5 Hz, NH), 3.76 (1 H, m, SJ = 43Hz, CHN), 3.65 (3
H, s, OCH3), 2.38 (2 H, t, J = 7.5 Hz, CH2CO); 1.82 (1 H, dtd, J =
14.0, 7.5, 5.0 Hz, CHAHB), 1.72 (1 H, q, J = 14.0, 7.5 Hz, CHAHB),
1.17 (3 H, d, J = 6.5 Hz, m, CH3).
Acknowledgement
This work was carried out with the financial support of Ministero
dell’Università e della Ricerca Scientifica e Tecnologica (MURST,
Italy).
13C NMR: d = 173.86 (s, COO), 155.82 (s, CON), 136.55, 128.49,
128.05 (s, 2 d, 3 d, C6H5), 66.56 (t, OCH2), 51.64 (q, OCH3), 46.92
(d, CHN), 31.95 (t, CH2CO), 30.80 (t, CH2), 21.30 (q, CH3).
Synthesis 1999, No. 5, 873–877 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Hydrogenation of g-Amino a,b-Unsaturated Esters in the Presence of Hydrogenable Protecting Groups
877
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Synthesis 1999, No. 5, 873–877 ISSN 0039-7881 © Thieme Stuttgart · New York