Click reaction on in situ generated β-azidostyrenes from cinnamic acid using CAN-NaN3: Synthesis of N-styryl triazoles

Article abstract of DOI:10.1016/j.tetlet.2011.01.129

N-Styryl triazoles are synthesized in one-pot starting with azido styrene obtained in situ from cinnamic acids and various acetylenes.

Full text of DOI:10.1016/j.tetlet.2011.01.129

Tetrahedron Letters 52 (2011) 1658–1662
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Tetrahedron Letters
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Click reaction on in situ generated b-azidostyrenes from cinnamic acid using
CAN–NaN3: synthesis of N-styryl triazoles
⇑
Mitta Kavitha, Bodugam Mahipal, Prathama S Mainkar, Srivari Chandrasekhar
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
N-Styryl triazoles are synthesized in one-pot starting with azido styrene obtained in situ from cinnamic
acids and various acetylenes.
Received 10 December 2010
Revised 21 January 2011
Accepted 27 January 2011
Available online 1 February 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Click reaction
Azidostyrenes
Cericammonium nitrate
Triazoles
One-pot reaction
‘Click’ chemistry has gained strong interest from both synthetic
and medicinal chemists, for constructing useful 1,2,3-triazole com-
pounds through Huisgen 1,3-dipolar cycloadditions of alkynes to
azides.1,2 It is one of the primary tools in conjugation of biopoly-
mers3 through triazole linker. There are several advantages in this
technique as a new chromophore is built for better fluorescence.4
Substituted triazoles show promise in small molecule synthesis
as new biological properties continue to unravel.5 Thus, the newer
methods for triazole synthesis continue to be a challenging propo-
sition. The ‘one-pot’ Domino processes provide an additional
advantage in reducing the number of steps and avoiding the isola-
tion of ‘not very stable’ intermediates.
Nair and George have reported a novel synthesis of b-azidosty-
renes involving the addition of NaN3 in the presence of cericammo-
nium nitrate (CAN) to cinnamic acid, which undergoes
decarboxylation at higher temperatures.6 This inspired us to ex-
plore the possibility of performing a direct ‘click reaction’ on cin-
namic acid under the described conditions while also adding
corresponding acetylenes and Cu turnings. Our assumption indeed
turned out to be a reality and the reaction medium was not adverse
for ‘click’ process.
ONO2
COOH
COOH
COOH
Ar
Ar
Ar
N3
N3
'Click'
N3
Product
Ar
Scheme 1. Intramolecular 1,3-dipolar cycloaddition.
In the first instance, cinnamic acid was subjected to a reaction
with CAN, NaN3, CH3COONa and acetylenic sugar derivative 2a
was added along with Cu turnings and CuSO4 solution to observe
the formation of sugar triazole 3a in 60% yield (Scheme 2). This
gave us confidence that the ‘in situ’ formation of vinyl azide fol-
lowed by ‘click reaction’ is proceeding smoothly.
Next, 2-O-propargyl ethyl cinnamate 2b was used as the acety-
lenic partner to get 3b in 63% yield (Table 1, entry 1). An attempt to
perform an intramolecular variant on the corresponding acid of 2-
O-propargyl cinnamic ester 2b resulted in a complex mixture of
products, which is rather disappointing. Further, the propargyl
ether 2c, obtained from 2-hydroxy ethylpropiolate, also underwent
smooth 3+2 cycloaddition with 2-azido styrene to provide the ad-
duct 3c in 65% yield (Table 1, entry 2). Other acetylenes, 2d–2g de-
rived from phenyl glycine, nicotinic acid, ibuprofen and
glyceraldehyde were well suited for the facile transformation to
generate N-styryl triazoles 3d–3g, respectively in over 60% yields
(Table 1, entries 3–6). The yields of the reactions are acceptable
considering the number of operations involved, addition of nitrate
and azido to olefin, elimination of HNO3, decarboxylation and
The sequence of reactions in ‘one-pot’ include, addition of –N3
and –ONO2 groups across double bond, elimination of HNO3 fol-
lowed by decarboxylation and ‘click reaction’ as depicted (Scheme
6
1) which is in accordance with Nair and George.
⇑
Corresponding author. Tel.: +91 40 27193210; fax: +91 40 27160512.
E-mail address: srivaric@iict.res.in (S. Chandrasekhar).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.01.129

M. Kavitha et al. / Tetrahedron Letters 52 (2011) 1658–1662
1659
N
1. CAN, NaN3, CH3CN, 10 h
2. CH3COONa, 60 o C, 2 h
N
COOH
N
O
O
Ph
AcO
AcO
1a
3a
O
O
AcO
3.
2a
AcO
60% yield, E/Z ratio 9:1
Cu turnings, Na Ascorbate,
Sat. CuSO4, 60 oC, 6 h
Scheme 2.
Table 1
One-pot synthesis of N-styryl triazoles from cinnamic acid (1a) using CAN–NaN3
a
Entry
Alkyne
Product
Time (h)
Yieldb (%)
E:Zc,d
COOEt
2b
COOEt
N
N
N
O
O
3b
1
5
63
90
88
Ph
EtO
O
O
EtO
O
O
N
N
N
2c
2
4
5
65
3c
Ph
N
NHBoc
O
NHBoc
O
N
N
3
4
60
65
85
52
Ph
O
O
O
O
3d
2d
N
O
O
N
2e
5
N
N
N
3e
Ph
O
O
O
N
N
N
2f
O
5
5
70
95
3f
Ph
N
N
N
Ph
3g
O
O
6
7
5
4
65
60
91
95
2g
2h
O
O
N
N
N
3h
Ph
N
N
2i
N
3i
8
4
60
90
Ph
(continued on next page)

1660
M. Kavitha et al. / Tetrahedron Letters 52 (2011) 1658–1662
Table 1 (continued)
Entry
Alkyne
Product
Time (h)
Yieldb (%)
E:Zc,d
N
N
N
Ph
3j
2j
9
4
60
60
O
NBoc
NBoc
O
a
Reaction conditions: CAN, NaN3, CH3CN, 10 h and CH3COONa, 60 °C, 2 h then alkyne, Cu turnings Na ascorbate, satd CuSo4, 60 °C, 4–6 h.
Isolated yields and the products were characterized by 13C NMR, IR and mass spectra.
E/Z ratio of inseperable products were estimated by 1H NMR.
b
c
d
Conditions not optimized for isolation of single geometric isomer.
Table 2
a
One-pot synthesis of 3-methoxy N-styryl triazoles from 3-methoxy cinnamic acid (1b) using CAN–NaN3
Entry
Alkyne
Product
Time (h)
Yieldb (%)
E:Zc
N
N
N
O
O
1
2b
5
67
90:10
3k
OMe
COOEt
O
N
N
N
3l
2
2f
5
71
52:48
OMe
N
N
N
2k
3
4
4
4
64
63
60:40
90:10
MeO
3m
MeO
OMe
N
N
N
3n
2l
N
Boc
N
Boc
OMe
a
b
c
Reaction conditions: CAN, NaH3, CH3CN, 10 h and CH3COONa, 60 °C, 2 h then alkyne, Cu turnings Na ascorbate, satd CuSo4, 60 °C, 4–6 h.
Isolated yields and the products were characterized by 13C NMR, IR and mass spectra.
E/Z ratio of inseparable products were estimated by 1H NMR.
cycloaddition (four-reactions). Other acetylenes such as 1-hexyne
2h, phenyl acetylene 2i and Garner aldehyde derivative 2j have
also produced the corresponding triazoles 3h–3j with consistent
yields (Table 1, entries 7–9). The formation of a major (E)-isomer
may be rationalized as a thermodynamically more stable product.
Also, the presence of copper metal in the reaction medium used for
the cycloaddition is known to catalyze isomerization of Z to E ste-
reoisomer.7 The result was further confirmed by performing the
cycloaddition reaction of vinyl azide obtained from 1a (1:1 mixture
as reported by Nair and George),6 wherein the major product was
the (E)-isomer as observed in the one-pot protocol.8
Similarly, the reaction of 3-methoxycinnamic acid 1b with dif-
ferent alkynes has also been successful in the formation of triazoles
(Table 2). The alkynes such as 2b, 2f, 3-methoxy phenyl acetylene
2k and indole derivative 2l with 3-methoxycinnamic acid have
produced 3-methoxy-N-styryl triazole derivatives 3k–3n, respec-
tively in over 65% yields (Table 2, entries 1–4).
triazoles may find applications in chemical biology and medicinal
chemistry.
Acknowledgment
M.K. and B.M. thank Council of Scientific and Industrial Re-
search (CSIR), New Delhi for research fellowship.
Supplementary data
Supplementary data (copies of 1H NMR and 13C NMR spectra for
all compounds) associated with this article can be found, in the on-
line version, at doi:10.1016/j.tetlet.2011.01.129.
References and notes
1. (a) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004–
2021; (b) Tornoe, C. M.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057–
3064; (c) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew.
Chem., Int. Ed. 2002, 41, 2596–2599; (d) Himo, F.; Lovell, T.; Hilgraf, R.;
Thus, a Domino process has been demonstrated for the click
reaction of cinnamic acid with various acetylenes.9 The resultant

M. Kavitha et al. / Tetrahedron Letters 52 (2011) 1658–1662
1661
Rostovtsev, V. V.; Noodleman, L.; Sharpless, K. B.; Fokin, V. V. J. Am. Chem. Soc.
2005, 127, 210–216.
1H), 1.4 (s, 9H); 13C NMR (75 MHz, CDCl3): dC 170.9, 154.8, 142.9, 136.1, 133.3,
128.9, 128.9, 128.8, 128.6, 127.2, 126.6, 122.7, 120.5, 80.3, 58.7, 57.8, 28.2; IR
2. (a) Huisgen, R. Angew. Chem. 1963, 75, 604–637; (b) Huisgen, R. Angew. Chem.
1963, 2, 565–598; (c) Huisgen, R. In Padwa, A., Ed.; 1,3-Dipolar Cycloaddition
Chemistry; Wiley: New York, 1984; pp 1–176; (d) Huisgen, R. Process Chem.
1961, 357–369; (e)Comprehensive Organic Synthesis; Trost, B. M., Ed.; Pergamon:
Oxford, 1991; Vol. 4, pp 1069–1109; for a review of asymmetric 1,3-dipolar
cycloaddition reactions, see (f) Gothelf, K. V.; Jorgensen, K. A. Chem. Rev. 1998,
98, 863–909; for a review of synthetic applications, see (g) Mulzer, J. Org. Synth.
Highlights 1991, 77–95.
3. Selected recent reviews; (a) Nandivada, H.; Jiang, X.; Lahann, J. Adv. Mater. 2007,
19, 2197–2208; (b) Angell, Y. L.; Burgess, K. Chem. Soc. Rev. 2007, 36, 1674–1689;
(c) Fournier, D.; Hoogenboom, R.; Schubert, U. S. Chem. Soc. Rev. 2007, 36, 1369–
1380; (d) Moses, J. E.; Moorhouse, A. D. Chem. Soc. Rev. 2007, 36, 1249–1262; (e)
Lutz, J.-F. Angew. Chem., Int. Ed. 2007, 46, 1018–1025; (f) Dondoni, A. Chem. Asian
J. 2007, 2, 700–708.
4. (a) Dyrager, C.; Börjesson, K.; Dinér, P.; Elf, A.; Albinsson, B.; Wilhelmsson, L. M.;
Grotli, M. Eur. J. Org. Chem. 2009, 1515–1521; (b) Scrafton, D. K.; Taylor, J. E.;
Mahon, M. F.; Fossy, J. S.; James, T. D. J. Org. Chem. 2008, 73, 2871–2874.
5. (a) Whiting, M.; Tripp, J. C.; Lin, Y. C.; Lindstrom, W.; Olson, A. J.; Elder, J. H.;
Sharpless, K. B.; Fokin, V. V. J. Med. Chem. 2006, 49, 7697–7710; (b) Youcef, R. A.;
Santos, M. D.; Roussel, S.; Baltaze, J. P.; Lubin-Germain, N.; Uziel, J. J. Org. Chem.
2009, 74, 4318–4323; (c) Sekiguchi, H.; Muranaka, K.; Osada, A.; Ichikawa, S.;
Matsuda, A. Bioorg. Med. Chem. 2010, 18, 5732–5737; (d) Junior, E. N. D. S.;
Guimaraes, T. T.; Menna-Barreto, R. F. S.; Pinto, M. D. C. F. R.; Simone, C. A. D.;
Pessoa, C.; Cavalcanti, B. C.; Sabino, J. R.; Andrade, C. K. Z.; Goulart, M. O. F.;
Castro, S. L. D.; Pinto, A. V. Bioorg. Med. Chem. 2010, 18, 3224–3230; (e) Kaval, N.;
Ermolat’ev, D.; Appukkuttan, P.; Dehaen, W.; Kappe, C. O.; Eycken, E. V. D. J.
Comb. Chem. 2005, 7, 490–502; (f) Tron, G. C.; Pirali, T.; Billington, R. A.;
Canonico, P. L.; Sorba, G.; Genazzani, A. A. Med. Res. Rev. 2008, 28, 278–308.
6. Nair, V.; George, T. G. Tetrahedron Lett. 2000, 41, 3199–3201.
(KBr): m ;
max 3439, 2975, 2928, 1711, 1495, 1238, 1163, 1048, 946, 750, 695 cmꢁ1
MS (ESI) m/z 435 (100) [M+H]+; HRMS calcd for C24H26N4NaO4 [M+Na]+:
457.1846; found, 457.185.
Compound 3e: semi solid; 1H NMR (300 MHz, CDCl3): dH 9.14 (s, 1H), 8.78 (s, 1H),
8.27 (dd, J = 8.3, 21.1 Hz, 1H), 8.04 (s, 1H), 7.73 (d, J = 15.1 Hz, 1H), 7.48–7.01 (m,
6H), 6.57 (d, J = 14.8 Hz, 1H), 5.52 (s, 1H), 5.38 (s, 1H); 13C NMR (75 MHz, CDCl3):
dC 153.5, 150.9, 150.8, 142.7, 142.1, 137.3, 137.2, 129.0, 128.99, 128.9, 128.4,
126.7, 124.6, 123.8, 123.4, 123.1, 122.7, 122.4, 121.5, 58.3, 58.1; IR (KBr): mmax
3449, 1725, 1638, 1280, 1112, 944, 741, 697 cmꢁ1; MS (ESI) m/z 307 (100)
[M+H]+; HRMS calcd for C17H15N4O2 [M+H]+: 307.119; found, 307.1192.
Compound 3f: solid; mp 90–92 °C; 1H NMR (500 MHz, CDCl3): dH 7.69–7.62 (m,
2H), 7.45–7.26 (m, 5H), 7.16 (d, J = 8.0 Hz, 2H), 7.10–7.02 (m, 3H), 5.23 (s, 2H),
3.69 (q, J = 6.6, 13.9 Hz, 1H), 2.42 (d, J = 7.3 Hz, 2H), 1.88–1.77 (m, 1H), 1.50 (d,
J = 7.3 Hz, 3H), 0.88 (d, J = 6.6 Hz, 6H); 13C NMR (75 MHz, CDCl3): dC 174.5, 143.3,
140.6, 137.2, 133.3, 129.3, 128.9, 128.8, 127.1, 126.6, 122.7, 122.0, 120.7, 57.8,
44.97, 44.91, 30.1, 22.3, 18.2; IR (KBr):
1150, 1013, 952, 753, 694 cmꢁ1; MS (ESI) m/z 390 (100) [M+H]+; HRMS calcd for
24H28N3O2[M+H]+: 390.2176; found, 390.216.
Compound 3g: solid; mp 102–104 °C;
= +4.5 (c 1.0, CHCl3); 1H NMR
mmax 2956, 2926, 1728, 1510, 1451, 1227,
C
½ ꢀ
a 2D8
(300 MHz, CDCl3): dH 7.82 (s, 1H), 7.71 (d, J = 14.7 Hz, 1H), 7.48–7.23 (m, 5H),
7.11 (d, J = 14.7 Hz, 1H), 5.28 (t, J = 6.6 Hz, 1H), 4.38 (t, J = 6.7 Hz, 1H), 4.01 (t,
J = 7.3 Hz, 1H), 1.76–1.53 (m, 8H), 1.52–1.35 (m, 2H); 13C NMR (75 MHz, CDCl3):
dC 148.3, 133.3, 129.0, 128.0, 126.7, 122.9, 121.9, 118.8, 110.7, 70.5, 69.4, 36.2,
35.1, 25.1; IR (KBr): mmax 2926, 1660, 1453, 1227, 1116, 1042, 951, 821,
692 cmꢁ1; MS (ESI) m/z 312 (100) [M+H]+; HRMS calcd for C18H22N3O2 [M+H]+:
312.1707; found, 312.1704.
Compound 3h: solid; mp 92–93 °C; 1H NMR (300 MHz, CDCl3): dH 8.31 (s, 1H),
7.73 (d, J = 14.35 Hz, 1H), 7.50–7.43 (m, 2H), 7.42–7.32 (m, 3H), 7.26 (d,
J = 14.9 Hz, 1H), 3.12 (t, J = 6.8 Hz, 2H), 1.87–1.75 (m, 2H), 1.4 (br s, 2H), 1.04 (t,
J = 7.55 Hz, 3H); 13C NMR (75 MHz, CDCl3): dC 132.9, 129.2, 129.0, 126.9, 123.9,
7. (a) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J. Org. Chem. 1991, 56, 6744–6746;
(b) Nozaki, H.; Nisikawa, Y.; Kawanisi, M.; Noyori, R. Tetrahedron 1967, 23,
2173–2179.
122.4, 122.2, 41.5, 29.6, 17.4, 13.7; IR (KBr): mmax 3445, 2961, 2086, 1678, 1634,
1529, 1450, 1253, 1128, 769, 693 cmꢁ1; MS (ESI) m/z 228 (100) [M+H]+; HRMS
8. The reaction of vinyl azide (E/Z 1:1) from 1a with 2a:
calcd for C14H18N3 [M+H]+ 228.1495; found, 228.1488.
O
O
N
AcO
AcO
N
N
N3
2a
O
O
Ph
AcO
AcO
Cu turnings, Na Ascorbate,
Sat. CuSO4, 60 oC, 6 h
3a
E/Z ratio 1:1
72% yield, E/Z ratio 9:1
9. General experimental procedure: To a deoxygenated solution of cinnamic acid
(1.0 mmol) and NaN3 (1.5 mmol) in dry acetonitrile (CH3CN), a deoxygenated
solution of CAN (2.5 mmol) in the same solvent was added dropwise at 0 °C and
the reaction temperature was raised to 25–30 °C. After stirring for 10 h at room
temperature, anhydrous sodium acetate (CH3COONa) (1.5 mmol) was added and
the reaction was heated to 65 °C. After stirring for 2 h, the alkyne compound
(0.9 mmol), copper turnings (10 mol%), CuSO4 solution (0.5 mL, 1 M) and
Compound 3i: solid; mp 96–98 °C; 1H NMR (300 MHz, CDCl3): dH 8.04 (s, 1H),
7.89–7.74 (m, 1H), 7.65 (d, J = 7.3 Hz, 2H), 7.43–7.28 (m, 6H), 7.27–7.19 (m, 2H),
6.53 (d, J = 9.6 Hz, 1H); 13C NMR (75 MHz, CDCl3): dC 128.9, 128.7, 128.4, 126.6,
125.8, 125.7, 123.4, 123.3, 123.0, 119.0, 116.5; IR (KBr): mmax 3450, 2925, 2108,
1705, 1632, 1456, 1313, 1269, 1176, 1044, 753, 688 cmꢁ1; MS (ESI) m/z 248
(100) [M+H]+; HRMS calcd for C16H14N3 [M+H]+: 248.1182.; found, 248.1176.
Compound 3j: solid; mp 96–98 °C; ½ ꢀ
a 2D5 = +27.4 (c 1.0, CHCl3); 1H NMR
sodium ascorbate (NaASc) (10 mol%) were added at
a time. The reaction
(300 MHz, CDCl3): dH 7.82–7.61 (m, 2H), 7.49–7.24 (m, 4H), 7.18–7.06 (m,
2H), 5.18–4.96 (m, 1H), 4.36–3.94 (m, 2H), 1.58 (s, 3H), 1.48 (s, 3H), 1.43–1.19
(m, 9H); 13C NMR (75 MHz, CDCl3): dC 159.8, 134.4, 130.0, 127.1, 123.5, 123.0,
121.1, 120.8, 119.8, 119.3, 118.3, 115.5, 114.7, 114.3, 114.2, 113.4, 111.9, 55.3,
mixture was refluxed (65 °C) for 4–6 h. After completion of the reaction
(monitored by TLC), the reaction mass was filtered through Celite. The volatiles
were removed on a rotary evaporator and subsequent column chromatography
over silica gel (60–120 mesh) gave E/Z inseperable mixture of triazoles in 60–
71% yields.
55.2, 29.7; IR (KBr): mmax 3458, 2979, 1693, 1658, 1388, 1378, 1255, 1172, 1093,
749, 694 cmꢁ1; MS (ESI) m/z 371 (100) [M+H]+; HRMS calcd for C20H27N4O3
[M+H]+: 371.2078; found, 371.2094.
Compound 3a: semi solid; ½a D30
ꢀ
= +56.5 (c 1.0, CHCl3); 1H NMR (300 MHz, CDCl3):
dH 7.89 (s, 1H), 7.74 (d, J = 14.7 Hz, 1H), 7.47–7.25 (m, 5H), 7.15 (d, J = 14.7 Hz,
1H), 5.92–5.77 (m, 2H), 5.29 (d, J = 9.6 Hz, 1H), 5.15 (br s, 1H), 4.91 (d,
J = 12.2 Hz, 1H), 4.75 (d, J = 12.2 Hz, 1H), 4.21–4.17 (m, 1H), 4.14–4.05 (m, 2H),
2.11–2.00 (m, 6H); 13C NMR (75 MHz, CDCl3): dC 170.5, 170.0, 143.9, 129.3,
128.7, 128.5, 128.3, 127.1, 123.7, 123.0, 122.2, 93.6, 93.3, 66.8, 65.0, 62.6, 60.8,
20.7, 20.6; IR (KBr): mmax 2951, 2107, 1742,1642, 1453, 1371, 1234, 1034, 768,
698 cmꢁ1; MS (ESI) m/z 414 (100) [M+H]+; HRMS calcd for C21H23N3NaO6
[M+Na]+: 436.1479; found, 436.149.
Compound 3k: solid; mp 96–98 °C; 1H NMR (300 MHz, CDCl3): dH 8.03–7.90 (m,
2H), 7.7 (d, J = 14.7 Hz, 1H), 7.50 (d, J = 7.7 Hz, 1H), 7.37–6.89 (m, 6H), 6.82 (d,
J = 8.1 Hz, 1H), 6.46 (d, J = 16.0 Hz, 1H), 5.34 (s, 2H), 4.24 (q, J = 7.0, 14.0 Hz, 2H),
3.82 (s, 3H), 1.33 (t, J = 7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3): dC 167.4, 156.6,
144.4, 139.6, 131.5, 130.0, 128.6, 123.0, 122.1, 121.5, 120.0, 119.3, 118.8, 114.5,
112.7, 112.0, 62.5, 60.4, 55.2, 14.3; IR (KBr): mmax 3450, 2925, 2108, 1705, 1632,
1456, 1313, 1269, 1176, 1044, 753, 688 cmꢁ1; MS (ESI) m/z 406 (100) [M+H]+;
HRMS calcd for C23H24N3O4 [M+H]+: 406.1761; found, 406.1781.
Compound 3b: solid; mp 96–98 °C; 1H NMR (300 MHz, CDCl3): dH 8.02–7.92 (m,
2H), 7.7 (d, J = 14.7 Hz, 1H), 7.24–7.52 (m, 7H), 7.15 (d, J = 14.7 Hz, 1H), 7.04 (d,
J = 8.3 Hz, 1H), 6.94 (t, J = 7.50 Hz, 1H), 6.46 (d, J = 16.5 Hz, 1H), 5.3 (s, 2H), 4.22
(q, J = 7.0, 14.0 Hz, 2H), 1.32 (t, J = 7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3): dC
167.3, 156.5, 144.3, 139.5, 133.3, 131.4, 129.0, 128.8, 128.5, 126.6, 122.7, 122.1,
121.4, 120.0, 118.8, 112.7, 62.5, 60.3, 14.2; IR (KBr): mmax 3410, 3077, 2924,
Compound 3l: semi solid; 1H NMR (300 MHz, CDCl3): dH 7.73–7.59 (m, 2H), 7.38–
6.84 (m, 7H), 6.76–6.50 (m, 2H), 5.29–5.05 (m, 2H), 3.88–3.80 (m, 3H), 3.76–3.68
(m, 1H), 2.48–2.39 (m, 2H), 1.91–1.75 (m, 1H), 1.54–1.40 (m, 3H), 0.94–0.81 (m,
6H); 13C NMR (75 MHz, CDCl3): dC 174.5, 174.2, 159.9, 159.8, 143.3, 142.6, 140.7,
140.6, 137.2, 134.7, 134.0, 130.0, 129.3, 129.2, 127.1, 127.0, 124.3, 123.3, 123.1,
123.0, 121.9, 120.7, 120.5, 119.2, 114.7, 114.4, 113.4, 112.9, 112.0, 57.7, 57.6,
55.2, 55.1, 49.8, 49.5, 44.9, 44.8, 30.1, 29.6, 29.3, 22.3, 18.3, 18.2; IR (KBr): mmax
3450, 2925, 2108, 1705, 1632, 1456, 1313, 1269, 1176, 1044, 753, 688 cmꢁ1; MS
(ESI) m/z 420 (100) [M+H]+; HRMS calcd for C25H30N3O3 [M+H]+: 420.2282;
found, 420.2293.
2955, 1904, 1711, 1632, 1451, 1313, 1272, 1162, 1036, 949, 866, 751,691 cmꢁ1
;
MS (ESI) m/z 376 (100) [M+H]+; HRMS calcd for C22H21N3NaO3 [M+Na]+:
398.1475; found, 398.1473.
Compound 3c: semi solid; ½a D30
ꢀ
= ꢁ28.2 (c 1.0, CHCl3); 1H NMR (300 MHz, CDCl3):
dH 7.88 (s, 1H), 7.65 (d, J = 15.1 Hz, 1H), 7.38–7.17 (m, 5H), 7.04 (d, J = 14.5 Hz,
1H), 4.7 (d, J = 12.0 Hz, 1H), 4.57 (d, J = 12.0 Hz, 1H), 4.18–4.00 (m, 3H), 1.34 (d,
J = 6.8 Hz, 3H), 1.22 (t, J = 6.8 Hz, 3H); 13C NMR (75 MHz, CDCl3): dC 172.8, 145.0,
133.3, 128.8, 128.6, 126.5, 122.7, 121.7, 120.1, 74.2, 63.2, 60.8, 18.4, 14.0; IR
(KBr): mmax 3467, 2938, 2077, 1738, 1634, 1453, 1210, 1117, 1023, 974, 751,
695 cmꢁ1; MS (ESI) m/z 302 (100) [M+H]+; HRMS calcd for C16H19N3O3 [M+Na]+:
324.1319; found, 324.1323.
Compound 3m: semi solid; 1H NMR (300 MHz, CDCl3): dH 7.59 (d, J = 9.0 Hz, 1H),
7.48 (s, 1H), 7.34–7.20 (m, 2H), 7.02–6.68 (m, 6H), 6.48 (d, J = 9.8 Hz, 1H), 3.81
(s, 3H), 3.71 (s, 3H); 13C NMR (75 MHz, CDCl3): dC 159.8, 141.2, 135.0, 134.4,
130.0, 127.2, 127.1, 123.5, 123.0, 121.1, 120.9, 118.3, 115.8, 115.5, 114.7, 114.3,
114.2, 113.4, 112.0, 55.3, 55.2; IR (KBr): mmax 3455, 2928, 2076, 1734, 1642,
1454, 1378, 1262, 1156, 773, 688 cmꢁ1; MS (ESI) m/z 308 (100) [M+H]+; HRMS
calcd for C18H18N3O2 [M+H]+: 308.1394; found, 308.1407.
Compound 3d: solid mp 108–110 °C; ½ ꢀ
a 2D8 = +1.3 (c 1.0, CHCl3); 1H NMR
Compound 3n: semi solid; 1H NMR (300 MHz, CDCl3): dH 8.17 (d, J = 8.3 Hz, 1H),
7.97 (s, 1H), 7.64 (s, 1H), 7.53 (d, J = 7.5 Hz, 1H), 7.38–7.16 (m, 4H), 6.93–6.81
(300 MHz, CDCl3): dH 7.69 (d, J = 6.7 Hz, 2H), 7.62 (s, 1H), 7.44–7.27 (m, 8H),
7.03 (d, J = 14.1 Hz, 1H), 5.60–5.45 (m, 1H), 5.39–5.21 (m, 3H), 4.17–4.02 (m,

1662
M. Kavitha et al. / Tetrahedron Letters 52 (2011) 1658–1662
(m, 2H), 6.73 (s, 1H), 6.54 (d, J = 9.82 Hz, 1H), 3.73 (s, 3H), 1.68 (s, 9H); 13C NMR
(75 MHz, CDCl3): dC 159.9, 149.4, 140.9, 135.6, 134.5, 130.0, 127.7, 124.7, 124.7,
29.6, 28.1; IR (KBr): mmax 3447, 2923, 2852, 2073, 1637, 1219, 1021, 771 cmꢁ1
;
MS (ESI) m/z 417 (100) [M+H]+; HRMS calcd for C24H24N4NaO3 [M+Na]+:
123.56, 123.5, 123.0, 120.8, 119.8, 119.4, 115.3, 114.5, 113.6, 110.9, 84.1, 55.2,
439.1741; found, 439.1717.