A mild and efficient catalytic mannich-type reaction as a simple access to N -benzyloxycarbonyl -amino ketones

Article abstract of DOI:10.1055/s-0029-1218728

N-Benzyloxycarbonylamino sulfones react with aromatic ketones in the presence of catalytic amount of boron trifluoride-diethyl ether at room temperature to afford the corresponding protected β-amino ketones in high yields (71-87%). Georg Thieme Verlag Stu

Full text of DOI:10.1055/s-0029-1218728

PAPER
2057
A Mild and Efficient Catalytic Mannich-Type Reaction as a Simple Access to
N-Benzyloxycarbonyl b-Amino Ketones1
A
Simple
Access
i
to
N
-
B
s
enzyloxyc
w
arbonyl
b
-Amino
a
K
etones nath Das,* Gandolla Chinna Reddy, Penagaluri Balasubramanyam, Boyapati Veeranjaneyulu
Organic Chemistry Division-1, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax +91(40)27193198; E-mail: biswanathdas@yahoo.com
Received 26 February 2010; revised 2 March 2010
Cbz
Cbz
O
Abstract: N-Benzyloxycarbonylamino sulfones react with aromat-
ic ketones in the presence of catalytic amount of boron trifluoride–
diethyl ether at room temperature to afford the corresponding pro-
tected b-amino ketones in high yields (71–87%).
NH
O
NH
BF3⋅OEt2
CH2Cl2, 25 °C
5–18 h
R2
+
Ph
R1
Ph
R1
SO2Tol
3
R2
1
2
R1 = aryl, alkyl
R2 = H, Me
71–87%
Key words: a-amido sulfones, stable imine precursors, aromatic
ketones, BF3·OEt2, Lewis acids, b-amino ketones
Scheme 1 Synthesis of N-benzyloxycarbonyl b-amino ketones
from N-benzyloxycarbonylamino sulfones
b-Amino carbonyl compounds exhibit significant biolog-
ical activity2 and their skeleton is present in different me-
dicinally important compounds.3 They are also valuable
building blocks for the synthesis of pharmaceuticals and
bioactive natural molecules.4 Paclitaxel, a prominent anti-
cancer compound, contains a b-amino carbonyl function
in its side chain, which is an important segment for its bio-
activity.5 The general protocol for the synthesis of b-ami-
no carbonyl compounds is the Mannich-type reaction of
aldehydes, amines (or directly imines), and enolizable ke-
tones or silyl enolates. Several methods have been devel-
oped involving these reactions,6 however, many of these
methods have different drawbacks, such as the use of tox-
ic reagents and expensive catalysts in excess, long reac-
tion times, drastic conditions, and unsatisfactory yields.
Moreover, several Lewis acid catalysts required to per-
form these Mannich-type reactions deactivate or decom-
pose in the presence of amines and water produced during
imine formation and many of the imines are unstable.
Here, we report the application of N-benzyloxycarbonyl-
amino sulfones for a simple and efficient synthesis of pro-
tected b-amino ketones.
catalyst. Subsequently this catalyst was used to prepare a
series of Cbz-protected b-amino ketones 3 (Table 2) fol-
lowing the above procedure (Scheme 1); earlier methods
for preparation of these compounds are limited.6,8
N-Benzyloxycarbonylamino sulfones 1 derived9 from
aromatic, heteroaromatic, and aliphatic aldehydes were
employed in this conversion; the aromatic aldehydes
contained both electron-donating and electron-withdraw-
ing groups. The reaction times required for the conversion
of the sulfones containing an aromatic ring with an elec-
tron-donating group into Cbz-protected b-amino ketones
3b–h were 5–10 hours. However, the conversion of N-
benzyloxycarbonylamino sulfones derived from aromatic
aldehydes with electron-withdrawing group or from ali-
phatic aldehydes into Cbz-protected b-amino ketones
3i,j,m,n required somewhat longer reaction times (15–18
h). The reaction conditions were mild and the products
3a–r were formed in high yields (71–87%). Different
functionalities, such as an ether, a halogen, and a nitro
group, remained intact. The sulfone prepared from a ster-
ically hindered aldehyde, such as 2-naphthaldehyde, un-
derwent the conversion smoothly to give 3k in 83% yield.
When the reaction was carried out with propiophenone
both anti- and syn-isomers were formed and these were
carefully separated; the anti-isomer was the major isomer.
The structures of all the products were confirmed by their
spectral data [IR, 1H and 13C NMR, ESI-MS, and HRMS
(ESI)]. The anti- and syn-isomers were characterized by
comparison of their 1H NMR spectral values with those of
In continuation of our work7 on the development of useful
synthetic methodologies using N-benzyloxycarbonylami-
no sulfones 1 (generally referred as a-amido sulfones) we
have found that the treatment of these compounds with ar-
omatic ketones 2 in the presence of a catalytic amount of
boron trifluoride–diethyl ether complex afforded the cor-
responding protected b-amino ketones 3 at room temper-
ature (Scheme 1).
1
known or related compounds.6,8,10 In the H NMR spec-
Initially N-benzyloxycarbonylamino sulfone 1a (R1 = Ph)
was treated with acetophenone (2a, R2 = H) at 25 °C in the
presence of various Lewis acids (Table 1). Consideration
of the reaction time and yield identified boron trifluoride–
diethyl ether complex (25 mol%) as the most effective
trum the coupling constant between H2 and H3 for the
anti-isomer is known to be 6–8 Hz while for a syn-isomer
it is 3–5 Hz. The NH proton of the anti-isomer also reso-
nates upfield (d = 5.0–5.5) compared to that of the syn-iso-
mer (d = 6.5–7.0).
Additionally, the anti- and syn-isomers were directly
compared with the authentic compounds prepared by our
earlier reported method.6f The N-Cbz group of the prod-
ucts can easily be deprotected11 to generate b-amino ke-
SYNTHESIS 2010, No. 12, pp 2057–2062
Advanced online publication: 12.04.2010
DOI: 10.1055/s-0029-1218728; Art ID: Z04710SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
1
0

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Table 1 Evaluation of the Catalytic Activity of Different Catalysts for the Preparation of N-Benzyloxycarbonyl b-Amino Ketones 3a,ia
Entry
a-Amido sulfone
b-Amino ketone
Catalyst
Time (h)
Yieldb (%)
BF3·OEt2
Cu(OTf)2
Bi(OTf)3
Yb(OTf)3
Sc(OTf)3
La(OTf)3
FeCl3
InCl3
ZrCl4
CuI
8
15
15
15
15
15
24
24
24
24
87
61
67
65
63
59
51
43
39
31
Cbz
NH
Cbz
NH
O
1
SO2Tol
Ph
BF3·OEt2
Cu(OTf)2
Bi(OTf)3
Yb(OTf)3
Sc(OTf)3
La(OTf)3
FeCl3
InCl3
ZrCl4
CuI
15
20
20
20
20
20
24
24
24
24
78
53
59
54
51
53
41
39
28
19
Cbz
NH
Cbz
NH
2
SO2Tol
NO2
SO2Tol
NO2
a Reaction conditions: a-amido sulfone 1 (1.0 mmol), acetophenone (2a, 1.2 mmol), catalyst (25 mol%), CH2Cl2 (5 mL), 25 °C, N2.
b Isolated yield.
The spectra were recorded with the following instruments; IR:
Perkin-Elmer RX1 FT-IR spectrophotometer; NMR: Varian Gemi-
ni 200 MHz (1H) and 50 MHz (13C) spectrometer; ESI-MS: VG-Au-
tospec micromass; and HRMS: QSTAR XL, Hybrid MS system
(Applied Biosystems). Column chromatography was performed
over silica gel (BDH 100–200 mesh). Solvents were purified ac-
cording to standard procedures. The silica gel F254 plates were used
for TLC.
tones. The free amine group can be utilized to synthesis
different analogues of the compounds. To our knowledge,
the present conversion is the first catalytic Mannich-type
reaction of N-benzyloxycarbonylamino sulfones with aro-
matic ketones. The only other report of such reaction of
these sulfones is known with silyl enolates in the presence
of bismuth(III) triflate.8,12
N-Benzyloxycarbonylamino sulfones can be easily
prepared9 from aldehydes and are generally stable solids.
They are known to be converted into the corresponding N-
acyliminium ions A (containing a positively charged ni-
trogen atom) on treatment with an appropriate Lewis acid.
Here, in the presence of boron trifluoride–diethyl ether
complex, N-benzyloxycarbonylamino sulfones were con-
verted into A which was then attacked by aromatic ke-
tones in the enolic form to produce the Cbz-protected b-
amino ketones (Scheme 2).
Benzyl 3-Oxo-3-diphenylpropylcarbamates 3; General Proce-
dure
To a soln of N-benzyloxycarbonylamino sulfone 1 (1.0 mmol) in
CH2Cl2 (5 mL) was added aromatic ketone (acetophenone or pro-
piophenone) 2 (1.2 mmol) under an N2 atmosphere. BF3·OEt2 (0.25
mmol) was added dropwise to this mixture, which was stirred at r.t.
(TLC monitoring). When the reaction was complete, the mixture
was washed with cold H2O (2 × 5 mL) and subsequently extracted
with EtOAc (2 × 10 mL). The extract was dried (anhyd Na2SO4)
and concentrated under vacuum. The residue was subjected to col-
umn chromatography (silica gel, 4–15% EtOAc–hexane) to give
pure 3.
In conclusion, we have developed a simple, mild, and ef-
ficient method for the synthesis of protected b-amino ke-
tones at room temperature and in high yields by treatment
of N-benzyloxycarbonylamino sulfones (prepared from
both aromatic and aliphatic aldehydes) with aromatic ke-
tones in the presence of boron trifluoride–diethyl ether
complex as a catalyst.
Benzyl 3-Oxo-1,3-diphenylpropylcarbamate (3a)
IR (KBr): 3371, 1721, 1680, 1525, 1449, 1290 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.90 (d, J = 8.0 Hz, 2 H), 7.52 (t,
J = 8.0 Hz, 1 H), 7.43 (d, J = 8.0 Hz, 2 H), 7.37–7.19 (m, 10 H),
5.85 (br s, 1 H), 5.30 (m, 1 H), 5.11 (d, J = 12.0 Hz, 1 H), 5.04 (d,
J = 12.0 Hz, 1 H), 3.70 (br d, J = 14.0 Hz, 1 H), 3.42 (dd, J = 14.0,
6.0 Hz, 1 H).
Cbz
Cbz
R
CbzNH2
ArSO2Na
NH
O
NH
Cbz
R
+
NH
BF3⋅OEt2
PhCOMe
RCHO
aq HCOOH
R
Ph
SO2Tol
A
Scheme 2 Formation of N-protected b-amino ketones through an N-acyliminium ion
Synthesis 2010, No. 12, 2057–2062 © Thieme Stuttgart · New York

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A Simple Access to N-Benzyloxycarbonyl b-Amino Ketones
2059
13C NMR (50 MHz, CDCl3): d = 197.8, 155.2, 136.6, 135.5 (d,
J = 10.0 Hz), 134.3, 128.0, 127.5, 126.8, 66.2, 50.3, 44.1.
MS (ESI): m/z = 378 [M + H]+.
Table 2 Synthesis of N-Benzyloxycarbonyl b-Amino Ketones 3 by
the Reaction of Various a-Amido Sulfones and Aromatic Ketones in
a
the Presence of BF3·OEt2
HRMS (ESI): m/z [M + Na]+ calcd for C23H20FNNaO3: 400.1324;
found: 400.1317.
Cbz
Cbz
O
NH
O
NH
BF3⋅OEt2
+
R2
R1
Ph
Ph
CH2Cl2, 25 °C
5–18 h
R1
SO2Tol
R2
Benzyl 1-(4-Chlorophenyl)-3-oxo-3-phenylpropylcarbamate
1
2
3
(3c)
71–87%
IR (KBr): 3334, 1696, 1499, 1250 cm–1.
Entry R1
R2
Product Time Yieldb Ratioc
1H NMR (200 MHz, CDCl3): d = 7.85 (d, J = 8.0 Hz, 2 H), 7.52 (t,
J = 8.0 Hz, 1 H), 7.40 (t, J = 8.0 Hz, 2 H), 7.36–7.19 (m, 9 H), 5.99
(d, J = 8.0 Hz, 1 H), 5.21 (m, 1 H), 5.08 (d, J = 12.0 Hz, 1 H), 5.02
(d, J = 12.0 Hz, 1 H), 3.67 (br d, J = 14.0 Hz, 1 H), 3.22 (dd,
J = 14.0, 6.0 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 198.2, 155.8, 140.0, 136.6, 136.5,
134.2, 134.0, 129.7, 128.6, 127.5, 127.2, 127.0, 66.2, 50.8, 44.3.
(h)
(%)
87
85
86
84
82
83
82
83
78
79
83
81
72
71
85
87
81
82
syn/anti
1
2
Ph
H
3a
3b
3c
3d
3e
3f
8
–
4-FC6H4
H
7
–
3
4-ClC6H4
4-BrC6H4
2-BrC6H4
4-MeC6H4
H
5
–
MS (ESI): m/z = 394, 396 [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C23H20ClNNaO3: 416.1029;
4
H
5
–
5
H
6
–
found: 416.1015.
6
H
9
–
Benzyl 1-(4-Bromophenyl)-3-oxo-3-phenylpropylcarbamate
7
4-EtO-3-MeOC6H3
3,4,5-(MeO)3C6H2
2-O2NC6H4
4-NCC6H4
H
3g
3h
3i
10
10
15
14
10
9
–
(3d)
IR (KBr): 3318, 1682, 1534, 1491, 1251 cm–1.
8
H
–
1H NMR (200 MHz, CDCl3): d = 7.84 (d, J = 8.0 Hz, 2 H), 7.53 (t,
J = 8.0 Hz, 1 H), 7.46–7.35 (m, 4 H), 7.31–7.18 (m, 7 H), 5.89 (br
s, 1 H), 5.20 (m, 1 H), 5.07 (d, J = 12.0 Hz, 1 H), 5.02 (d, J = 12.0
Hz, 1 H), 3.69 (br d, J = 14.0 Hz, 1 H), 3.34 (d, J = 14.0, 6.0 Hz, 1
H).
13C NMR (50 MHz, CDCl3): d = 198.0, 155.1, 140.1, 135.8, 134.2,
130.7, 129.8, 128.0, 127.5, 127.3, 126.6, 66.2, 50.7, 44.6.
9
H
–
10
11
12
13
14
15
16
17
18
H
3j
–
2-naphthyl
H
3k
3l
–
2-thienyl
H
–
MS (ESI): m/z = 438, 440 [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C23H20BrNNaO3: 460.0524;
cyclohexyl
H
3m
3n
3o
3p
3q
3r
17
18
7
–
CH2CHMe2
4-FC6H4
H
–
found: 460.0508.
Me
Me
45:55
39:61
48:52
45:55
Benzyl 1-(2-Bromophenyl)-3-oxo-3-phenylpropylcarbamate
(3e)
4-ClC6H4
7
IR (KBr): 3330, 1695, 1541, 1450, 1275 cm–1.
3,4,5-(MeO)3C6H2 Me
2-naphthyl Me
10
10
1H NMR (200 MHz, CDCl3): d = 7.89 (d, J = 8.0 Hz, 2 H), 7.60–
7.21 (m, 11 H), 7.09 (t, J = 8.0 Hz, 1 H), 6.29 (br s, 1 H), 5.61 (m,
1 H), 5.11 (d, J = 12.0 Hz, 1 H), 5.02 (d, J = 8.0 Hz, 1 H), 3.72 (br
d, J = 14.0 Hz, 1 H), 3.45 (dd, J = 14.0, 4.0 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 199.5, 155.2, 136.2, 134.2, 134.0,
129.8, 129.6, 129.5, 128.7, 127.9, 66.0, 51.4, 41.2.
MS (ESI): m/z = 438, 440 [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C23H20BrNNaO3: 460.0524;
a Reaction conditions: a-amido sulfone 1 (1.0 mmol), acetophenone or
propiophenone 2 (1.2 mmol), catalyst (25 mol%), CH2Cl2 (5 mL), 25
°C, N2.
b Isolated yield.
c Ratio syn/anti-isomers determined by 1H NMR spectroscopy
13C NMR (50 MHz, CDCl3): d = 196.8, 156.2, 141.5, 135.9, 135.8,
134.4, 129.1, 128.5, 127.3, 126.4, 66.6, 51.7, 43.9.
MS (ESI): m/z = 360 [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C23H21NNaO3: 382.1419;
found: 460.0532.
Benzyl 3-Oxo-3-phenyl-1-(4-tolyl)propylcarbamate (3f)
IR (KBr): 3378, 1720, 1682, 1530, 1447, 1290 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.90 (d, J = 8.0 Hz, 2 H), 7.55 (t,
J = 8.0 Hz, 1 H), 7.42 (t, J = 8.0 Hz, 2 H), 7.79–7.28 (br s, 5 H), 7.22
(d, J = 8.0 Hz, 2 H), 7.10 (d, J = 8.0 Hz, 2 H), 5.82 (br s, 1 H), 5.30
(m, 1 H), 5.11 (d, J = 12.0 Hz, 1 H), 5.02 (d, J = 12.0 Hz, 1 H), 3.70
(br d, J = 14.0 Hz, 1 H), 3.42 (dd, J = 14.0, 6.0 Hz, 1 H), 2.29 (s, 3
H).
13C NMR (50 MHz, CDCl3): d = 197.6, 155.4, 138.0, 136.8, 136.0,
135.9, 134.4, 129.8, 129.0, 128.1, 125.4, 66.2, 51.4, 44.6, 20.3.
MS (ESI): m/z = 374 [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C24H23NNaO3: 396.1575;
found: 382.1407.
Benzyl 1-(4-Fluorophenyl)-3-oxo-3-phenylpropylcarbamate
(3b)
IR (KBr): 3337, 1691, 1510, 1451, 1225 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.89 (d, J = 8.0 Hz, 2 H), 7.57 (t,
J = 8.0 Hz, 1 H), 7.41 (t, J = 8.0 Hz, 2 H), 7.35–7.22 (br s, 7 H),
7.04–6.90 (m, 2 H), 5.89 (br s, 1 H), 5.29 (m, 1 H), 5.11 (d, J = 12.0
Hz, 1 H), 5.04 (d, J = 12.0 Hz, 1 H), 3.62 (dd, J = 14.0, 4.0 Hz, 1
H), 3.41 (dd, J = 14.0, 6.0 Hz, 1 H).
found: 396.1572.
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Benzyl 1-(4-Ethoxy-3-methoxyphenyl)-3-oxo-3-phenylpropyl-
carbamate (3g)
1H NMR (200 MHz, CDCl3): d = 7.88 (d, J = 8.0 Hz, 2 H), 7.75–
7.69 (m, 4 H), 7.54–7.20 (m, 11 H), 6.05 (d, J = 8.0 Hz, 1 H), 5.42
(m, 1 H), 5.10 (d, J = 12.0 Hz, 1 H), 5.02 (d, J = 12.0 Hz, 1 H), 3.77
(br d, J = 14.0 Hz, 1 H), 3.48 (d, J = 14.0, 6.0 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 197.2, 155.8, 139.1, 136.2, 136.1,
133.7, 133.2, 129.0, 128.1, 127.4, 126.3, 126.2, 125.2, 125.0, 66.4,
51.2, 42.8.
IR (KBr): 3343, 1716, 1593, 1513, 1454, 1260 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.89 (d, J = 8.0 Hz, 2 H), 7.51 (t,
J = 8.0 Hz, 1 H), 7.42 (t, J = 8.0 Hz, 2 H), 7.35–7.21 (br s, 5 H),
6.90–6.69 (m, 3 H), 5.74 (br s, 1 H), 5.20 (m, 1 H), 5.11 (d, J = 12.0
Hz, 1 H), 5.02 (d, J = 12.0 Hz, 1 H), 4.02 (q, J = 7.0 Hz, 2 H), 3.80
(s, 3 H), 3.69 (br d, J = 14.0 Hz, 1 H), 3.36 (dd, J = 14.0, 6.0 Hz, 1
H), 1.40 (t, J = 7.0 Hz, 3 H).
13C NMR (50 MHz, CDCl3): d = 198.6, 156.8, 153.8, 148.0, 137.2,
134.8, 134.6, 127.6, 127.5, 127.3, 118.2, 112.5, 110.4, 66.0, 54.9,
55.1, 51.8, 44.9, 14.9.
MS (ESI): m/z = 410 [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C27H23NNaO3: 432.1575;
found: 432.1577.
Benzyl 3-Oxo-3-phenyl-1-(thiophen-2-yl)propylcarbamate (3l)
MS (ESI): m/z = 434 [M + H]+.
IR (KBr): 3339, 1692, 1522, 1450, 1223 cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C26H27NNaO5: 456.1786;
found: 456.1768.
1H NMR (200 MHz, CDCl3): d = 7.92 (d, J = 8.0 Hz, 2 H), 7.55 (t,
J = 8.0 Hz, 1 H), 7.44 (t, J = 8.0 Hz, 2 H), 7.39–7.22 (br s, 5 H), 7.12
(m, 1 H), 6.93 (m, 1 H), 6.90 (m, 1 H), 5.95 (br s, 1 H), 5.54 (m, 1
H), 5.08 (s, 2 H), 3.76 (br d, J = 14.0 Hz, 1 H), 3.49 (dd, J = 14.0,
6.0 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 198.2, 155.1, 145.1, 135.8, 135.6,
138.3, 128.7, 127.8, 127.5, 126.4, 124.9, 66.2, 46.4, 44.8.
Benzyl 3-Oxo-3-phenyl-1-(3,4,5-trimethoxyphenyl)propylcar-
bamate (3h)
IR (KBr): 3357, 1694, 1593, 1507, 1458, 1237 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.90 (d, J = 8.0 Hz, 2 H), 7.55 (t,
J = 8.0 Hz, 1 H), 7.44 (t, J = 8.0 Hz, 2 H), 7.35–7.22 (br s, 5 H), 6.50
(s, 2 H), 5.80 (br s, 1 H), 5.16 (m, 1 H), 5.07 (s, 2 H), 3.79 (s, 6 H),
3.74 (s, 3 H), 3.61 (br d, J = 14.0 Hz, 1 H), 3.32 (dd, J = 14.0, 6.0
Hz, 1 H).
MS (ESI): m/z = 366 [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C21H19NNaO3S: 388.0983;
found: 388.0988.
13C NMR (50 MHz, CDCl3): d = 198.4, 155.2, 154.1, 137.5, 137.2,
136.9, 134.0, 129.5, 129.0, 128.3, 102.5, 66.2, 60.1, 55.8, 51.4,
43.4.
MS (ESI): m/z = 450 [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C26H27NNaO6: 472.1736;
Benzyl 1-Cyclohexyl-3-oxo-3-phenylpropylcarbamate (3m)
IR (KBr): 3441, 1702, 1504, 1449, 1216 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.92 (d, J = 8.0 Hz, 2 H), 7.58 (t,
J = 8.0 Hz, 1 H), 7.48 (d, J = 8.0 Hz, 2 H), 7.35–7.28 (br s, 5 H),
5.32 (d, J = 8.0 Hz, 1 H), 5.04 (s, 2 H), 3.91 (m, 1 H), 3.33 (dd,
J = 14.0, 6.0 Hz, 1 H), 3.12 (dd, J = 14.0, 4.0 Hz, 1 H), 1.90 (m, 1
H), 1.71–1.53 (m, 7 H), 1.32–1.11 (m, 2 H), 1.01 (m, 1 H).
found: 472.1741.
Benzyl 1-(2-Nitrophenyl)-3-oxo-3-phenylpropylcarbamate (3i)
13C NMR (50 MHz, CDCl3): d = 199.7, 156.1, 135.8, 134.2, 129.2,
IR (KBr): 3328, 1688, 1524, 1338, 1264 cm–1.
129.0, 128.4, 66.0, 53.4, 40.6, 40.1, 30.1, 29.9, 29.8, 25.4, 25.2.
1H NMR (200 MHz, CDCl3): d = 8.00–7.89 (m, 3 H), 7.76 (d,
J = 8.0 Hz, 1 H), 7.65–7.52 (m, 2 H), 7.49–7.38 (m, 3 H), 7.36–7.25
(br s, 5 H), 6.38 (d, J = 8.0 Hz, 1 H), 5.80 (m, 1 H), 5.08 (d, J = 12.0
Hz, 1 H), 5.01 (d, J = 12.0 Hz, 1 H), 3.72–3.59 (m, 2 H).
MS (ESI): m/z = 388 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C23H27NNaO3: 388.1888;
found: 388.1891.
13C NMR (50 MHz, CDCl3): d = 198.5, 156.0, 148.2, 136.2, 135.8,
Benzyl 5-Methyl-1-oxo-1-phenylhexan-3-ylcarbamate (3n)
134.5, 134.2, 130.4, 129.3, 129.2, 129.0, 125.1, 65.9, 49.2, 42.3.
IR (KBr): 3359, 1715, 1510, 1224 cm–1.
MS (ESI): m/z = 405 [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C23H20N2NaO5: 427.1269;
1H NMR (200 MHz, CDCl3): d = 7.96 (d, J = 8.0 Hz, 2 H), 7.56 (t,
J = 8.0 Hz, 1 H), 7.45 (t, J = 8.0 Hz, 2 H), 7.39–7.30 (m, 5 H), 5.32
(d, J = 8.0 Hz, 1 H), 5.09 (s, 2 H), 4.21 (m, 1 H), 3.35 (dd, J = 14.0,
4.0 Hz, 1 H), 3.12 (dd, J = 14.0, 6.0 Hz, 1 H), 1.40 (m, 1 H), 1.29–
1.16 (m, 2 H), 0.87 (d, J = 7.0 Hz, 6 H).
found: 427.1285.
Benzyl 1-(4-Cyanophenyl)-3-oxo-3-phenylpropylcarbamate
(3j)
13C NMR (50 MHz, CDCl3): d = 196.5, 155.7, 134.0, 130.1, 130.0,
IR (KBr): 3421, 1691, 1528, 1452, 1254 cm–1.
129.9, 129.8, 128.4, 125.5, 65.7, 45.4, 43.8, 29.9, 25.1, 24.0, 21.3.
1H NMR (200 MHz, CDCl3): d = 7.89 (d, J = 8.0 Hz, 2 H), 7.64–
7.29 (m, 12 H), 6.10 (br s, 1 H), 5.36 (m, 1 H), 5.11 (d, J = 12.0 Hz,
1 H), 5.03 (d, J = 12.0 Hz, 1 H), 3.70 (br d, J = 14.0 Hz, 1 H), 3.47
(dd, J = 14.0, 6.0 Hz, 1 H).
MS (ESI): m/z = 340 [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C21H25NNaO3: 362.1732;
found: 362.1725.
13C NMR (50 MHz, CDCl3): d = 198.1, 155.2, 146.0, 135.2, 133.8,
132.2, 128.8, 128.2, 127.9, 127.5, 126.0, 118.7, 110.2, 66.0, 50.7,
44.1.
MS (ESI): m/z = 385 [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C24H20N2NaO3: 407.1371;
Benzyl (1S,2S)-1-(4-Fluorophenyl)-2-methyl-3-oxo-3-phenyl-
propylcarbamate (syn-3o)
IR (KBr): 3357, 1692, 1533, 1448, 1262 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.75 (d, J = 8.0 Hz, 2 H), 7.51 (t,
J = 8.0 Hz, 1 H), 7.43–7.29 (m, 7 H), 7.25–7.20 (m, 2 H), 6.92 (t,
J = 8.0 Hz, 2 H), 6.66 (br s, 1 H), 5.12 (d, J = 12.0 Hz, 1 H), 5.08
(d, J = 12.0 Hz, 1 H), 5.03 (m, 1 H), 4.01 (m, 1 H), 1.33 (d, J = 7.0
Hz, 3 H).
found: 407.1375.
Benzyl 1-(Naphthalen-2-yl)-3-oxo-3-phenylpropylcarbamate
(3k)
13C NMR (50 MHz, CDCl3): d = 199.8, 164.6, 160.1, 155.7, 135.8,
135.6, 134.1, 128.7, 128.2, 127.5, 115.0 (d, J = 10.0 Hz), 65.8, 56.1,
44.9, 15.2.
IR (KBr): 3344, 1697, 1513, 1455, 1250 cm–1.
Synthesis 2010, No. 12, 2057–2062 © Thieme Stuttgart · New York

PAPER
A Simple Access to N-Benzyloxycarbonyl b-Amino Ketones
2061
MS (ESI): m/z = 414 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C24H22FNNaO3: 414.1481;
1H NMR (200 MHz,CDCl3): d = 7.82 (d, J = 8.0 Hz, 2 H), 7.59–
7.22 (m, 8 H), 6.39 (s, 2 H), 5.21–4.94 (m, 4 H), 3.96 (m, 1 H), 3.72
(s, 9 H), 1.21 (d, J = 7.0 Hz, 3 H).
13C NMR (50 MHz, CDCl3): d = 201.8, 156.1, 154.2, 135.8, 135.7,
133.2, 130.8, 130.1, 130.0, 129.7, 129.5, 128.6, 128.5, 104.5, 66.0,
60.6, 57.2, 55.8, 45.6, 14.7.
MS (ESI): m/z = 464 [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C27H29NNaO6: 486.1887;
found: 414.1484.
Benzyl (1S,2R)-1-(4-Fluorophenyl)-2-methyl-3-oxo-3-phenyl-
propylcarbamate (anti-3o)
IR (KBr): 3359, 1692, 1510, 1223 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.86 (d, J = 8.0 Hz, 2 H), 7.56 (t,
J = 8.0 Hz, 1 H), 7.41 (t, J = 8.0 Hz, 2 H), 7.35–7.20 (m, 7 H), 6.92
(t, J = 8.0 Hz, 2 H), 5.29 (t, J = 8.0 Hz, 1 H), 5.14 (t, J = 8.0 Hz, 1
H), 5.10 (d, J = 12.0 Hz, 1 H), 5.01 (d, J = 12.0 Hz, 1 H), 3.98 (m,
1 H), 1.23 (d, J = 8.0 Hz, 3 H).
13C NMR (50 MHz, CDCl3): d = 201.2, 164.4, 160.1, 155.6, 136.4,
136.3, 132.8, 128.5, 128.2, 127.9, 115.1 (d, J = 10.0 Hz), 65.9, 55.2,
45.7, 14.5.
found: 486.1899.
Benzyl (1S,2S)-2-Methyl-1-(naphthalen-2-yl)-3-oxo-3-phenyl-
propylcarbamate (syn-3r)
IR (KBr): 3420, 1685, 1533, 1452, 1242 cm–1.
1H NMR (200 MHz,CDCl3): d = 7.86–7.65 (m, 6 H), 7.51–7.22 (m,
11 H), 6.73 (br s, 1 H), 5.20 (m, 1 H), 5.08 (s, 2 H), 4.11 (m, 1 H),
1.32 (d, J = 7.0 Hz, 3 H).
MS (ESI): m/z = 414 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C24H22FNNaO3: 414.1481;
found: 414.1496.
13C NMR (50 MHz, CDCl3): d = 204.7, 155.6, 139.3, 136.1, 136.0,
133.8, 133.7, 132.5, 129.0, 128.2, 128.0, 127.5, 127.2, 125.8, 125.7,
125.3, 124.9, 66.3, 58.2, 44.9, 15.6.
Benzyl (1S,2S)-1-(4-Chlorophenyl)-2-methyl-3-oxo-3-phenyl-
propylcarbamate (syn-3p)
MS (ESI): m/z = 424 [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C28H25NNaO3: 446.1732;
IR (KBr): 3314, 1702, 1673, 1533, 1239 cm–1.
found: 446.1728.
1H NMR (200 MHz, CDCl3): d = 7.75 (d, J = 8.0 Hz, 2 H), 7.52 (t,
J = 8.0 Hz, 1 H), 7.41–7.23 (m, 7 H), 7.20 (br s, 4 H), 6.62 (br s, 1
H), 5.10 (s, 2 H), 5.01 (m, 1 H), 4.00 (m, 1 H), 1.32 (d, J = 7.0 Hz,
3 H).
13C NMR (50 MHz, CDCl3): d = 204.2, 155.8, 140.1, 135.6, 135.5,
134.1, 133.3, 129.0, 128.2, 127.5, 66.1, 56.3, 44.9, 15.4.
MS (ESI): m/z = 408, 410 [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C24H22ClNNaO3: 430.1185;
Benzyl (1S,2R)-2-Methyl-1-(naphthalen-2-yl)-3-oxo-3-phenyl-
propylcarbamate (anti-3r)
IR (KBr): 3341, 1693, 1527, 1452, 1213 cm–1.
1H NMR (200 MHz,CDCl3): d = 7.85 (d, J = 8.0 Hz, 2 H), 7.81–
7.67 (m, 4 H), 7.55–7.23 (m, 11 H), 5.40–5.24 (m, 2 H), 5.03 (d,
J = 12.0 Hz, 1 H), 4.97 (d, J = 12.0 Hz, 1 H), 4.10 (m, 1 H), 1.22 (d,
J = 7.0 Hz, 3 H).
13C NMR (50 MHz, CDCl3): d = 201.6, 155.8, 135.6, 134.0, 133.8,
129.4, 129.1, 128.7, 128.6, 128.2, 125.9, 125.7, 125.1, 66.0, 56.2,
45.1, 14.2.
found: 430.1178.
Benzyl (1S,2R)-1-(4-Chlorophenyl)-2-methyl-3-oxo-3-phenyl-
propylcarbamate (anti-3p)
MS (ESI): m/z = 424 [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C28H25NNaO3: 446.1732;
IR (KBr): 3343, 1694, 1528, 1283, 1239 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.83 (d, J = 8.0 Hz, 2 H), 7.56 (t,
J = 8.0 Hz, 1 H), 7.42 (t, J = 8.0 Hz, 2 H), 7.34–7.12 (m, 9 H), 5.22
(br s, 1 H), 5.11–4.94 (m, 3 H), 3.93 (m, 1 H), 1.20 (d, J = 7.0 Hz,
3 H).
13C NMR (50 MHz, CDCl3): d = 201.6, 155.8, 139.9, 135.7, 135.6,
133.6, 133.5, 129.1, 129.0, 128.4, 66.3, 55.8, 45.1, 14.2.
found: 446.1725.
Acknowledgment
The authors thank CSIR and UGC, New Delhi for financial assis-
tance. They are also thankful to NMR, Mass, and IR Divisions of
IICT for spectral recording.
MS (ESI): m/z = 408, 410 [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C24H22ClNNaO3: 430.1185;
found: 430.1199.
References
Benzyl (1S,2S)-2-Methyl-3-oxo-3-phenyl-1-(3,4,5-trimethoxy-
phenyl)propylcarbamate (syn-3q)
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7.21 (m, 8 H), 6.60 (br s, 1 H), 6.39 (s, 2 H), 5.10 (s, 2 H), 4.91 (m,
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