Regio- and stereoselective synthesis of α,β amino esters

Article abstract of DOI:10.3184/030823408X338684

A facile method for the regio- and stereoselective synthesis of α,β-dehydro-β-amino esters from acetates of Baylis- Hillman adducts with amines was reported. In the absence of any solvent and catalyst, the present strategy works well for a series of electron deficient and electron rich aromatic amines as well as aliphatic ones.

Full text of DOI:10.3184/030823408X338684

434 RESEARCH PAPER
AUGUST, 434–436
JOURNAL OF CHEMICAL RESEARCH 2008
Regio- and stereoselective synthesis of D,E-dehydro-E-amino esters
Dafeng Li, Jian Li and Xueshun Jia*
Department of Chemistry, Shanghai University, Shanghai 200444, P.R. China
A facile method for the regio- and stereoselective synthesis of D,E-dehydro-E-amino esters from acetates of Baylis-
Hillman adducts with amines was reported. In the absence of any solvent and catalyst, the present strategy works
well for a series of electron deficient and electron rich aromatic amines as well as aliphatic ones.
Keywords %D\OLV±+LOOPDQꢀDGGXFWꢁꢀDPLQHꢁꢀĮꢁȕꢂGHK\GURꢂȕꢂDPLQRꢀHVWHUꢁꢀVROYHQWꢂIUHHꢁꢀFDWDO\VWꢂIUHH
Įꢁȕꢂ'HK\GURꢂȕꢂDPLQRꢀHVWHUVꢀDUHꢀLPSRUWDQWꢀEXLOGLQJꢀEORFNVꢀIRUꢀ
the synthesis of indenoquinoline derivatives, nonproteinogenic
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of modern medicines.1-4ꢀ3HSWLGHꢀGHULYDWLYHVꢀRIꢀĮꢁȕꢂGHK\GURꢂ
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amino acids can provide constraint after incorporation into a
peptide molecule and thus renders a peptide more favourable
to bonding to its target.9,10ꢀ1RWHꢀWKDWꢀWKHꢀȕꢂDPLQRꢀDFLGVꢀRIWHQꢀ
require synthesis when they are not available commercially.11
Hence, the development of various methodologies for the
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esters has been disclosed.12-28,7 Among these protocols, using
readily available Baylis–Hillman adducts as substrates provide
a practical and straightforward choice. However, many suffer
from long reaction times, low regioselectivity and low yields,
the basic conditions, and the use of harmful solvents. Recently,
SDOODGLXPꢂFDWDO\VHGꢀV\QWKHVLVꢀRIꢀĮꢁȕꢂGHK\GURꢂȕꢂDPLQRꢀHVWHUVꢀ
from Baylis–Hillman adducts with amines contributes an
interesting procedure, but the shortage of this approach is the
use of expensive palladium reagent, air-sensitive phosphine
ligand as well as inert atmosphere.7ꢀ 5HFHQWO\ꢁꢀ ĮꢁȕꢂGHK\GURꢂ
ȕꢂDPLQRꢀ HVWHUVꢀ KDYHꢀ DOVRꢀ EHHQꢀ V\QWKHVLVHGꢀ IURPꢀ DFHWDWHVꢀ
of Baylis–Hillman adducts with amines in the presence of
cerium (IV) ammonium nitrate at nitrogen atmosphere.20 So,
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Baylis–Hillman adducts are of valuable synthetic
intermediates for the synthesis of a number of complex
molecules, biologically active molecules as well as natural
products.29-38 Recently, we have described applications of
Baylis–Hillman adducts and many excellent results were
also demonstrated.39-44 As a continuation of our previous
work, herein, we disclose a facile, regio- and stereoselective
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Baylis–Hillman acetates with various primary amines under
the catalyst- and solvent-free conditions. (Scheme 1). To the
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2a under solvent- and catalyst-free conditions, and the mixture
was then stirred at 80°C until reaction completion. This model
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GHK\GURꢂȕꢂDPLQRꢀHVWHUꢀ3a was afforded in 91% yield (Table 1,
entry 1). Furthermore, high E-stereoselectivity was observed
from the 1H NMR spectrum of 3a. In contrast, when CH3CN
and THF were used as solvent in this model reaction, 3a is
obtained in 83% and 70% yields respectively together with
prolonged reaction time (2 h). During our investigation, we
also found that the reaction temperature played an important
role and the reaction became quite sluggish together with low
yields at room temperature.
Encouraged by these experimental results, a series of
anilines 1 were treated with Baylis–Hillman adducts 2 at 80°C
under catalyst- and solvent-free conditions. As shown in Table
1, various aromatic amines underwent smooth conversion
WRꢀ FRUUHVSRQGLQJꢀ ĮꢁȕꢂGHK\GURꢂȕꢂDPLQRꢀ HVWHUV 3a–l in good
to excellent yields. Note that the behaviour of the present
strategy is quite dependent on the type of substrate anilines.
The substituent groups of anilines affected the conversion
dramatically. As we can see, electron-donating groups such
as methyl and methoxy groups add the nucleophilicity of
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1–3, 6–9). In contrast, the presence of electron-withdrawing
groups such as chloro and bromo groups obviously decreased
the nucleophilicity of aromatic amines and the conversion
became more sluggish (entries 10–12). In addition, the good
E-stereoselectivity was demonstrated in most cases and no
side products were observed. Apart from the electronic effect,
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to disappear completely (entries 6–8).
To establish the generality of the present transformation,
a series of aliphatic amines were then tested with Baylis–
Hillman adducts. Blending of 1.5 mmol of benzylamine 1g
and 1 mmol of Baylis–Hillman adduct 2a at room temperature
UHVXOWHGꢀLQꢀWKHꢀIRUPDWLRQꢀRIꢀERWKꢀĮꢁȕꢂGHK\GURꢂȕꢂDPLQRꢀHVWHUꢀ
and bis-allylic tertiary amine in 45 and 50% yield respectively.
Indeed, the aliphatic substrate was so reactive that the
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the enhanced nucleophilicity of amino group. Subsequently,
various experimental parameters including temperature and
substrate ratio were screened. We found that the excessive use
Initially, we used p-methoxyaniline 1a and Baylis–Hillman
adduct 2a as model substrate. In a typical experiment,
1.5 mmol of 1a was added to 1 mmol of Baylis–Hillman adduct
OAc
neat
COOMe
NHR'
COOMe
R
R
+
R'NH2
rt or 80 °C
1
2
3
R = aryl; R' = alkyl, aryl
Scheme 1
* Correspondent. E-mail: xsjia@mail.shu.edu.cn

JOURNAL OF CHEMICAL RESEARCH 2008 435
Table 1 Regioselective synthesis of D,E-dehydro-E-amino estersa
Entry
Amine 1
R
Time
Yield/%b
Product
E/Zc
1
2
4-MeOC6H4NH2
4-MeOC6H4NH2
4-MeOC6H4NH2
C6H4NH2
Ph
0.5 h
0.5 h
0.5 h
2 h
91
93
98
88
90
82
90
87
95
92
83
91
95
93
93
92
96
83
97
3a
3b
3c
3d
3e
3f
3g
3h
3i
92:8
93: 7
4-MeC6H4
4-ClC6H4
4-ClC6H4
4-NO2C6H4
Ph
3
93:7
4
77:23
70:30
93:7
5
C6H4NH2
2 h
6
2-MeOC6H4NH2
2-MeOC6H4NH2
2-MeOC6H4NH2
4-MeC6H4NH2
4-ClC6H4NH2
4-ClC6H4NH2
4-BrC6H4NH2
C6H5CH2NH2
C6H5CH2NH2
C6H5CH2NH2
C6H5(CH3)CHNH2
t-BuNH2
2 h
7
4-MeC6H4
4-ClC6H4
4-ClC6H4
4-NO2C6H4
4-MeOPh
4-NO2C6H4
Ph
2 h
86:14
85:15
80:20
80:20
84:16
82:18
95:5
8
2 h
9
2 h
10
11
12
13
14
15
16
17
18
19
4 h
3j
3k
3l
4 h
4 h
2 min
2 min
2 min
2 min
2 min
2 min
2 min
3m
3n
3o
3p
3q
3r
4-MeC6H4
4-ClC6H4
Ph
93:7
90:10
100:0
100:0
86:14
86:14
Ph
Cyclohexylamine
(CH3)2CHNH2
Ph
Ph
3s
aMethod A: the reaction of aromatic amines with Baylis–Hillman adducts.
Method B: the reaction of aliphatic amines with Baylis–Hillman adducts.
bIsolated yields. c The ratio was determined by the 1H NMR spectrum.
3d: Oil (lit.21); IR (KBr)/cm-1: 3393, 1709, 1631; 1H NMR
(500 MHz, CDCl3) 7.80 (s, 1H), 7.37 (d, 2H, Jꢀ ꢀꢍꢃꢏꢀ+]ꢉꢁꢀꢌꢃꢄꢄꢀꢆGꢁꢀ
2H, Jꢀ ꢀꢍꢃꢏꢀ+]ꢉꢁꢀꢌꢃꢇꢐ±ꢌꢃꢇꢄꢀꢆPꢁꢀꢄ+ꢉꢁꢀꢐꢃꢏꢄꢀꢆGꢁꢀꢈ+ꢁꢀJ ꢀꢍꢃꢏꢀ+]ꢉꢁꢀꢎꢃꢅꢐꢀꢆVꢁꢀ
2H), 3.81 (s, 3H).
of benzylamine 1g ꢆꢄꢀHTXLYꢃꢉꢀFRXOGꢀIRUPꢀĮꢁȕꢂGHK\GURꢂȕꢂDPLQRꢀ
ester exclusively. Then, several structurally diversed aliphatic
primary amines experienced the similar conversion (Table 1,
1g–k). As can be seen, the excellent chemoselectivity and the
good stereoselectivity were achieved in all cases (Table 1,
3m–s).
In conclusion, we have developed a facile, regio- and
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good to excellent yields from the reaction of various primary
amines with Baylis–Hillman adducts under solvent- and
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its use in organic synthesis, especially in large-scale industrial
preparation.
3e: Oil; IR (KBr)/cm-1: 3396, 1713, 1637; 1H NMR (500
MHz, CDCl3) 8.22 (d, 2H, Jꢀ ꢀꢑꢃꢅꢀ+]ꢉꢁꢀꢌꢃꢍꢌꢀꢆVꢁꢀꢇ+ꢉꢁꢀꢌꢃꢏꢑꢀꢆGꢁꢀꢈ+ꢁꢀ
Jꢀ ꢀꢑꢃꢅꢀ+]ꢉꢁꢀꢌꢃꢇꢏ±ꢌꢃꢇꢄꢀꢆPꢁꢀꢄ+ꢉꢁꢀꢐꢃꢏꢈꢀꢆGꢁꢀꢈ+ꢁꢀJ ꢀꢌꢃꢏꢀ+]ꢉꢁꢀꢎꢃꢅꢌꢀꢆVꢁꢀꢈ+ꢉꢁꢀ
3.85 (s, 3H). Anal. Calcd for C17H16N2O4: C, 65.37; H, 5.16; N, 8.96.
Found: C, 65.19; H, 5.25; N, 8.79.
3f: Oil; IR (KBr)/cm-1: 3409, 1709, 1630; 1H NMR (500 MHz,
CDCl3ꢉꢀįꢀꢆSSPꢉꢋꢀꢌꢃꢑꢅꢀꢆVꢁꢀꢇ+ꢉꢁꢀꢌꢃꢎꢏ±ꢌꢃꢄꢐꢀꢆPꢁꢀꢏ+ꢉꢁꢀꢐꢃꢍꢅ±ꢐꢃꢐꢍꢀꢆPꢁꢀꢄ+ꢉꢁꢀ
6.45 (d, 2H, J ꢀꢌꢃꢏꢀ+]ꢉꢁꢀꢎꢃꢇꢈꢀꢆVꢁꢀꢈ+ꢉꢁꢀꢄꢃꢍꢇꢀꢆVꢁꢀꢄ+ꢉꢁꢀꢄꢃꢍꢈꢀꢆVꢁꢀꢄ+ꢉꢃꢀ$QDOꢃꢀ
Calcd for C18H19NO3: C, 72.70; H, 6.44; N, 4.71. Found: C, 72.91;
H, 6.21; N, 4.86.
3g: Oil; IR (KBr)/cm-1: 3407, 1714, 1628; 1H NMR (500 MHz,
CDCl3ꢉꢀįꢀꢆSSPꢉꢋꢀꢌꢃꢍꢅꢀꢆVꢁꢀꢇ+ꢉꢁꢀꢌꢃꢈꢍꢀꢆGꢁꢀꢈ+ꢁꢀJ ꢀꢍꢃꢏꢀ+]ꢉꢁꢀꢌꢃꢅꢑꢀꢆGꢁꢀꢈ+ꢁꢀ
J ꢀꢍꢃꢏꢀ+]ꢉꢁꢀꢐꢃꢍꢅ±ꢐꢃꢏꢑꢀꢆPꢁꢀꢄ+ꢉꢁꢀꢐꢃꢎꢅꢀꢆGꢁꢀꢇ+ꢁꢀJ ꢀꢌꢃꢏꢀ+]ꢉꢁꢀꢎꢃꢅꢎꢀꢆVꢁꢀꢈ+ꢉꢁꢀ
3.73 (s, 3H), 3.72 (s, 3H), 2.27 (s, 3H). Anal. Calcd for C19H21NO3:
C, 73.28; H, 6.79; N, 4.49. Found: C, 73.50; H, 6.86; N, 4.33.
3h: Oil; IR (KBr)/cm-1: 3379, 1717, 1634; 1H NMR (500 MHz,
CDCl3ꢉꢀįꢀꢆSSPꢉꢋꢀꢌꢃꢍꢎꢀꢆVꢁꢀꢇ+ꢉꢁꢀꢌꢃꢎꢅꢀꢆGꢁꢀꢈ+ꢁꢀJ ꢀꢍꢃꢏꢀ+]ꢉꢁꢀꢌꢃꢄꢎꢀꢆGꢁꢀꢈ+ꢁꢀ
J ꢀꢍꢃꢏꢀ+]ꢉꢁꢀꢐꢃꢍꢄ±ꢐꢃꢌꢅꢀꢆPꢁꢀꢄ+ꢉꢁꢀꢐꢃꢎꢐꢀꢆGꢁꢀꢈ+ꢁꢀJ ꢀꢐꢃꢏꢀ+]ꢉꢁꢀꢎꢃꢅꢍꢀꢆVꢁꢀꢈ+ꢉꢁꢀ
3.85 (s, 3H), 3.83 (s, 3H). Anal. Calcd for C18H18ClNO3: C, 65.15; H,
5.46; N, 4.22. Found: C, 65.30; H, 5.19; N, 4.39.
Experimental
All 1H NMR spectra were measured in CDCl3 and recorded on
Bruker AC – 500 (500 MHz) spectrometer with TMS as the internal
standard. IR spectra were measured with a Perkin–Elmer FT-IR-1600
spectrometer. Elemental analyses were performed on Elemantar Vario
EL instrument.
General procedure
3i: Oil; IR (KBr)/cm-1: 3391, 1709, 1617; 1H NMR (500 MHz,
CDCl3ꢉꢀįꢀꢆSSPꢉꢋꢀꢌꢃꢍꢅꢀꢆVꢁꢀꢇ+ꢉꢁꢀꢌꢃꢄꢍꢀꢆGꢁꢀꢈ+ꢁꢀJ ꢀꢍꢃꢏꢀ+]ꢉꢁꢀꢌꢃꢄꢄꢀꢆGꢁꢀꢈ+ꢁꢀ
J ꢀꢍꢃꢏꢀ+]ꢉꢁꢀꢐꢃꢑꢐꢀꢆGꢁꢀꢈ+ꢁꢀJ ꢀꢍꢃꢏꢀ+]ꢉꢁꢀꢐꢃꢎꢐꢀꢆGꢁꢀꢈ+ꢁꢀJ ꢀꢍꢃꢏꢀ+]ꢉꢁꢀꢎꢃꢅꢎꢀ
(s, 2H), 3.81(s, 3H), 2.23 (s, 3H). Anal. Calcd for C18H18ClNO2: C,
68.46; H, 5.74; N, 4.43. Found: C, 68.71; H, 5.54; N, 4.26.
3j: Oil; IR (KBr)/cm-1: 3390, 1709, 1634; 1H NMR (500 MHz,
CDCl3ꢉꢀįꢀꢆSSPꢉꢋꢀꢍꢃꢈꢎꢀꢆGꢁꢀꢈ+ꢁꢀJ ꢀꢍꢃꢏꢀ+]ꢉꢁꢀꢌꢃꢍꢍꢀꢆVꢁꢀꢇ+ꢉꢁꢀꢌꢃꢏꢌꢀꢆGꢁꢀꢈ+ꢁꢀ
J ꢀꢍꢃꢏꢀ+]ꢉꢁꢀꢌꢃꢈꢏꢀꢆGꢁꢀꢈ+ꢁꢀJ ꢀꢍꢃꢏꢀ+]ꢉꢁꢀꢐꢃꢄꢐꢀꢆGꢁꢀꢈ+ꢁꢀJ ꢀꢍꢃꢏꢀ+]ꢉꢁꢀꢎꢃꢅꢏꢀꢆVꢁꢀ
2H), 3.86 (s, 3H). Anal. Calcd for C17H15ClN2O4: C, 58.88; H, 4.35;
N, 8.07. Found: C, 58.63; H, 4.10; N, 8.27.
Method A: To magnetically stirred 1.5 mmol of aromatic amines 1
in an oven-dried glassware, 1 mmol of Baylis–Hillman adducts 2
was added. The mixtures were stirred at 80°C until the completion
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silica gel column chromatography eluting with hexane/ethyl acetate
to afford the corresponding products (3a–l). All of the products were
LGHQWL¿HGꢀE\ꢀ,5ꢀDQGꢀ1H NMR spectra. The new compounds were also
LGHQWL¿HGꢀE\ꢀHOHPHQWDOꢀDQDO\VLVꢃ
Method B: To magnetically stirred 3 mmol of aliphatic amines 1
in an oven-dried glassware, 1 mmol of Baylis–Hillman adducts 2
was added. The mixtures were stirred at room temperature until the
completion of reactions (monitored by TLC). Then the mixture was
SXUL¿HGꢀE\ꢀVLOLFDꢀJHOꢀFROXPQꢀFKURPDWRJUDSK\ꢀHOXWLQJꢀZLWKꢀKH[DQHꢊ
ethyl acetate to afford the corresponding products (3m–s). All of
WKHꢀSURGXFWVꢀZHUHꢀLGHQWL¿HGꢀE\ꢀ,5ꢀDQGꢀ1H NMR spectra. The new
FRPSRXQGVꢀZHUHꢀDOVRꢀLGHQWL¿HGꢀE\ꢀHOHPHQWDOꢀDQDO\VLVꢃ
3k: Oil; IR (KBr)/cm-1: 3386, 1699, 1629; 1H NMR (500 MHz,
CDCl3ꢉꢀįꢀꢆSSPꢉꢋꢀꢌꢃꢍꢍꢀꢆVꢁꢀꢇ+ꢉꢁꢀꢌꢃꢎꢄꢀꢆGꢁꢀꢈ+ꢁꢀJ ꢀꢑꢃꢅꢀ+]ꢉꢁꢀꢌꢃꢇꢇꢀꢆGꢁꢀꢈ+ꢁꢀ
J ꢀꢑꢃꢅꢀ+]ꢉꢁꢀꢐꢃꢑꢇꢀꢆGꢁꢀꢈ+ꢁꢀJ ꢀꢑꢃꢅꢀ+]ꢉꢁꢀꢐꢃꢎꢏꢀꢆGꢁꢀꢈ+ꢁꢀJ ꢀꢑꢃꢅꢀ+]ꢉꢁꢀꢎꢃꢅꢑꢀ
(s, 2H), 3.81 (s, 3H), 3.82 (s, 3H). Anal. Calcd for C18H18ClNO3: C,
65.15; H, 5.46; N, 4.22. Found: C, 65.28; H, 5.31; N, 4.59.
3l: Oil; IR (KBr)/cm-1: 3381, 1705, 1599; 1H NMR (500 MHz,
CDCl3ꢉꢀįꢀꢆSSPꢉꢋꢀꢍꢃꢈꢎꢀꢆGꢁꢀꢈ+ꢁꢀJ ꢀꢍꢃꢏꢀ+]ꢉꢁꢀꢌꢃꢍꢍꢀꢆVꢁꢀꢇ+ꢉꢁꢀꢌꢃꢏꢌꢀꢆGꢁꢀꢈ+ꢁꢀ
J ꢀꢍꢃꢏꢀ+]ꢉꢁꢀꢌꢃꢅꢌꢀꢆGꢁꢀꢈ+ꢁꢀJ ꢀꢑꢃꢅꢀ+]ꢉꢁꢀꢐꢃꢎꢇꢀꢆGꢁꢀꢈ+ꢁꢀJ ꢀꢑꢃꢅꢀ+]ꢉꢁꢀꢎꢃꢅꢏꢀꢆVꢁꢀ
2H), 3.86 (s, 3H). Anal. Calcd for C17H15BrN2O4: C, 52.19; H, 3.86;
N, 7.16. Found: C, 52.39; H, 3.65; N, 7.32.
3a: Oil (lit.7); IR(KBr)/cm-1: 3383, 1709, 1625; 1H NMR (500 MHz,
CDCl3ꢉꢀ įꢀ ꢆSSPꢉꢋꢀ ꢌꢃꢍꢌꢀ ꢆVꢁꢀ ꢇ+ꢉꢁꢀ ꢌꢃꢎꢏ±ꢌꢃꢄꢌꢀ ꢆPꢁꢀ ꢏ+ꢉꢁꢀ ꢐꢃꢌꢄꢀ ꢆGꢁꢀ ꢈ+ꢁꢀ
J ꢀꢑꢃꢅꢀ+]ꢉꢁꢀꢐꢃꢏꢅꢀꢆGꢁꢀꢈ+ꢁ J ꢀꢑꢃꢅꢀ+]ꢉꢁꢀꢄꢃꢍꢇꢀꢆVꢁꢀꢄ+ꢉꢁꢀꢄꢃꢌꢈꢀꢆVꢁꢀꢄ+ꢉꢃ
3b: IR (KBr)/cm-1: 3380, 1694, 1605; 1H NMR (500 MHz, CDCl3)
įꢀꢆSSPꢉꢋꢀꢌꢃꢍꢎꢀꢆVꢁꢀꢇ+ꢉꢁꢀꢌꢃꢄꢏꢀꢆGꢁꢀꢈ+ꢁ Jꢀ ꢀꢍꢃꢅꢀ+]ꢉꢁꢀꢌꢃꢇꢑꢀꢆGꢁꢀꢈ+ꢁ Jꢀ ꢀꢍꢃꢅꢀ
Hz), 6.74 (d, 2H, Jꢀ ꢀꢑꢃꢅꢀ+]ꢉꢁꢀꢐꢃꢏꢈꢀꢆGꢁꢀꢈ+ꢁ Jꢀ ꢀꢑꢃꢅꢀ+]ꢉꢁꢀꢎꢃꢅꢌꢀꢆVꢁꢀꢈ+ꢉꢁꢀ
3.81 (s, 3H), 3.73 (s, 3H), 2.36 (s, 3H). Anal. Calcd for C19H21NO3:
C, 73.28; H, 6.79; N, 4.49. Found: C, 73.53; H, 6.62; N, 4.69.
3c: Oil (lit.7); IR (KBr)/cm-1: 3387, 1696, 1621; 1H NMR
(500 MHz, CDCl3) 7.79 (s, 1H), 7.39 (d, 2H, Jꢀ ꢀꢍꢃꢏꢀ+]ꢉꢁꢀꢌꢃꢄꢏꢀꢆGꢁꢀꢈ+ꢁ
Jꢀ ꢀꢍꢃꢏꢀ+]ꢉꢁꢀꢐꢃꢌꢏꢀꢆGꢁꢀꢈ+ꢁꢀJꢀ ꢀꢑꢃꢅꢀ+]ꢉꢁꢀꢐꢃꢏꢇꢀꢆGꢁꢀꢈ+ꢁꢀJꢀ ꢀꢑꢃꢅꢀ+]ꢉꢁꢀꢎꢃꢅꢈꢀꢆVꢁꢀ
2H), 3.82 (s, 3H), 3.73 (s, 3H).
1
3m: Oil (lit.20); IR (KBr)/cm-1: 3333, 1707, 1628; H NMR (500
MHz, CDCl3ꢉꢀįꢀꢆSSPꢉꢋꢀꢌꢃꢍꢇꢀꢆVꢁꢀꢇ+ꢉꢁꢀꢌꢃꢎꢄ±ꢌꢃꢈꢏꢀꢆPꢁꢀꢇꢅ+ꢉꢁꢀꢄꢃꢍꢈꢀꢆVꢁꢀ
3H), 3.81(s, 2H), 3.59 (s, 2H), 2.04 (brs, 1H).
3n: Oil (lit.20); IR (KBr)/cm-1: 3332, 1703, 1629; 1H NMR(500
MHz, CDCl3ꢉꢀįꢀꢆSSPꢉꢋꢀꢌꢃꢍꢄꢀꢆVꢁꢀꢇ+ꢉꢁꢀꢌꢃꢄꢑ±ꢌꢃꢄꢐꢀꢆPꢁꢀꢌ+ꢉꢁꢀꢌꢃꢇꢌꢀꢆGꢁꢀꢈ+ꢁꢀ
J ꢀꢍꢃꢅꢀ+]ꢉꢁꢀꢄꢃꢍꢐꢆVꢁꢀꢈ+ꢉꢁꢀꢄꢃꢍꢏꢆVꢁꢀꢄ+ꢉꢁꢀꢄꢃꢐꢏꢆVꢁꢀꢈ+ꢉꢁꢀꢈꢃꢎꢅꢀꢆVꢁꢀꢄ+ꢉꢁꢀꢈꢃꢇꢈꢀ
(brs, 1H).

436 JOURNAL OF CHEMICAL RESEARCH 2008
3o: Oil (lit.7); IR (KBr)/cm-1: 3330, 1709, 1630; 1H NMR
(500 MHz, CDCl3ꢉꢀįꢀꢆSSPꢉꢋꢀꢌꢃꢌꢈꢀꢆVꢁꢀꢇ+ꢉꢁꢀꢌꢃꢄꢌ±ꢌꢃꢇꢑꢀꢆPꢁꢀꢑ+ꢉꢁꢀꢄꢃꢍꢇꢀꢆVꢁꢀ
3H), 3.80 (s, 2H),3.53 (s, 2H), 2.06 (brs, 1H).
protein; B. Weinstein, ed., Marcel Dekker: New York, 1982; Vol. IV, p.3.
11 J. Kimura, Y. Takada, T. Inayoshi, Y. Nakao, G. Goetz, W.Y. Yoshida and
P.J. Scheuer, J. Org. Chem., 2002, 67, 1760.
12 H. Chen, L.N. Patkar, S. Ueng, C. Lin and A.S. Lee, Synlett, 2005, 2035.
13 F. Andre and E.G. Farid, Bull. Soc. Chim. Fr., 1989, 403.
14 J. Itoh, K. Fuchibe and T. Akiyama, Synthesis, 2008, 1319.
15 M. Grzegorz, R. Jaroslaw, L. Anthony and H. Heinz, Helv. Chim. Acta,
1997, 80, 1992.
3p: Oil; IR (KBr)/cm-1: 3324, 1703, 1631; 1H NMR (500 MHz,
CDCl3) (ppm): 7.76 (s, 1H), 7.39–7.19 (m, 10H), 3.82 (s, 3H), 3.77
(q, 1H, J ꢀꢐꢃꢏ Hz), 3.47 (d, 1H, J ꢀꢇꢈ Hz), 3.41 (d, 1H, J ꢀꢇꢈ Hz),
2.01 (brs, 1H), 1.38 (d, 3H, Jꢀ ꢀꢌꢃꢅ Hz). Anal. Calcd for C19H21NO2:
C, 77.25; H, 7.16; N, 4.74. Found: C, 77.15; H, 7.33; N, 4.69.
3q: Oil (lit.26); IR (KBr)/cm-1: 3424, 1719, 1633; 1H NMR
(500 MHz, CDCl3) 7.79 (s, 1H), 7.58 (d, 2H, Jꢀ ꢀꢌꢃꢅ Hz), 7.39–7.34
(m, 3H), 3.82 (s, 3H), 3.53 (s, 2H), 1.65 (brs, 1H), 1.16 (s, 9H).
3r: Oil (lit.20); IR (KBr)/cm-1: 3320, 1707, 1631; 1H NMR
(500 MHz, CDCl3) (ppm): 7.82 (s, 1H), 7.51 (d, 2H, Jꢀ ꢀꢐꢃꢏ Hz),
7.41–7.21 (m, 3H), 3.83 (s, 3H), 3.62 (s, 2H), 2.46 (m, 1H), 1.82 (brs,
1H), 1.73–1.20 (m, 10H).
16 D. Biswanath, M. Gurram, C. Nikhil and B. Joydeep, Synlett, 2005,
1000.
17 M. Martin and J. Hans, Liebigs Ann. Chem., 1986, 533.
18 N.N. Sergeeva, A.S. Golubev, L. Hennig, M. Findeisen, E. Paetzold,
G. Oehme and K. Burger, J. Fluorine Chem., 2001, 111, 41.
19 B.A. Kulkarmi and A. Ganesan, J. Combinat. Chem., 1999, 1, 373.
20 M. Paira, S. Kumar, M. Subhas and C. Roy, Tetrahedron Lett., 2008, 49,
2432.
21 C.G. Lee, K.Y. Lee, S. GowriSankar and J.N. Kim, Tetrahedron Lett.,
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3s: Oil (lit.45); IR (KBr)/cm-1: 3324, 1708, 1632; 1H NMR(500
MHz, CDCl3) (ppm): 7.80 (s, 1H), 7.51 (d, 2H, Jꢀ ꢀꢌꢃꢏ Hz), 7.41–
7.37 (m, 3H), 3.82 (s, 3H), 3.59 (s, 2H), 2.83 (m, 1H), 1.91 (brs, 1H),
1.05 (d, 6H, Jꢀ ꢀꢐꢃꢏꢀ+]ꢉꢃ
22 J.N. Kim, H.J. Lee, K.Y. Lee and J.H. Gong, Synlett, 2002, 173.
23 J.N. Kim, H.S. Kim, G.H. Gong and Y.M. Chung, Tetrehedron Lett., 2001,
42, 8341.
24 Y.S. Park, M.Y. Cho, Y.B. Kwon, B.W. Yoo and C.M. Yoon, Synth.
Commun., 2007, 37, 2677.
The authors thank the National Natural Science Foundation
of China (No: 20572068) and Innovation Fund of Shanghai
8QLYHUVLW\ꢀIRUꢀ¿QDQFLDOꢀVXSSRUWꢃ
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27 B.C. Ranu, S. Samanta and S.K. Guchhait, Tetrehedron, 2002, 58, 983.
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29 D. Basavaiah, A.J. Rao and T. Satyanarayana, Chem. Rev., 2003, 103,
811.
Received 28 May 2008; accepted 20 June 2008
Paper 08/5297 doi: 10.3184/030823408X338684
Published online: 27 August 2008
30 P.V. Ramachandran, S. Madhi, L. Bland-Berry, M.V.R. Reddy and
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