Alkynylation of N-tosylimines with aryl acetylenes promoted by ZnBr 2 and N,N-diisopropylethylamine in acetonitrile

Article abstract of DOI:10.1016/j.tetlet.2004.11.046

We found a suitable condition for the effective alkynylation of N-tosylimines with aryl acetylenes. The reaction of N-tosylimines and aryl acetylenes in the presence of ZnBr₂ and DIEA (N,N- diisopropylethylamine) in CH₃CN afforded the desired N-tosyl propargylamines in moderate to good yields.

Full text of DOI:10.1016/j.tetlet.2004.11.046

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 69–74
Alkynylation of N-tosylimines with aryl acetylenes promoted by
ZnBr2 and N,N-diisopropylethylamine in acetonitrile
Ka Young Lee, Chang Gon Lee, Jeong Eun Na and Jae Nyoung Kim*
Department of Chemistry and Institute of Basic Sciences, Chonnam National University, Kwangju 500-757, South Korea
Received 8 September 2004; revised 20 October 2004; accepted 5 November 2004
Abstract—We found a suitable condition for the effective alkynylation of N-tosylimines with aryl acetylenes. The reaction of N-
tosylimines and aryl acetylenes in the presence of ZnBr2 and DIEA (N,N-diisopropylethylamine) in CH3CN afforded the desired
N-tosyl propargylamines in moderate to good yields.
Ó 2004 Elsevier Ltd. All rights reserved.
The addition reaction of nucleophiles to C@O bond of
carbonyl compounds and C@N bond of imines and their
derivatives has received much attention to organic
chemists. Synthesis of propargylic alcohols and prop-
argylic amines is one of the major topics in recent years
due to the usefulness in synthetic organic chemistry as
synthetic intermediates and their variety biological
activities.1 For the introduction of triple bond, metal
acetylide has been used usually, which was generated
in situ from terminal acetylenic compound and n-BuLi
or EtMgBr.2a Recently, acetylide ion was generated
and used in the alkynylation of ketones and aldehydes
by the use of cesium hydroxide2b or nonmetallic benzyl-
trimethylammonium hydroxide.2c However, such pro-
cesses have some drawbacks. The reaction usually
must be carried out under anhydrous conditions with
much caution. Due to the strongly basic nature or nucleo-
philicity of the n-BuLi, EtMgBr or quaternary ammo-
nium hydroxide, the reaction may cause some side
reactions.
Lewis acids such as ZnCl2, Zn(OTf)2, ZnBr2, InBr3,
CuBr, GaI3, Sn(OTf)2 were used with or without the
combination of amines depending on the used
reagents.4–6 As the electrophilic components,
aldehydes,4a,b,f,g,6b imines,4c,6a N-acyliminium salts,4e
a,b-unsaturated carbonyls,4d,5d and nitrones3 have been
studied. However, to our best knowledge, another
reactive electrophile, N-tosylimine7 was not examined.
Carreira and co-workers have reported only one exam-
ple of the reaction of N-tosylimine and phenylacetylene
in their Zn(OTf)2-mediated synthesis of N-hydroxy
propargylic amine derivatives.3
In some cases, N-tosylimine showed higher electrophil-
icity than the corresponding aldehyde or imine. Thus,
we presumed that we could prepare the corresponding
N-tosyl propargylamine compounds by applying the
newly developing concept3,4 if we successfully find out
suitable Lewis acid and amine catalyst combination
(Scheme 1). Fortunately, we could find a good condition
for the synthesis of N-tosyl propargylamines and wish to
report herein the results.
Recently, Carreira and co-workers have reported a mild
procedure for the addition reaction of acetylenic com-
pound to nitrones involving the in situ generated zinc
acetylide in the presence of a tertiary amine.3 The con-
cept has been extended further by many chemists.4–6
Initially, we screened a variety of combinations as
shown in Table 1 by using 2-chlorobenzaldehyde N-
tosylimine (1a) and phenylacetylene (2a) as the represen-
tative examples. The use of indium chloride (entry 1)
and zinc chloride (entry 2) was found ineffective. The
use of catalytic amounts of zinc bromide (entry 3) gave
low yield of product 3a. The reaction at room tempera-
ture with zinc bromide failed completely (entry 4). The
use of THF (entry 7) or benzene (entry 8) was found
Keywords: Alkynylation; N-Tosylimines; Aryl acetylenes; ZnBr2;
DIEA.
*
Corresponding author. Tel.: +82 62 530 3381; fax: +82 62 530
3389; e-mail: kimjn@chonnam.ac.kr
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.11.046

70
K. Y. Lee et al. / Tetrahedron Letters 46 (2005) 69–74
Ts
H
N
Ts
N
+
Cl
Cl
2a
1a
3a
Scheme 1.
Table 1. Optimization of reaction conditions for 3a from 1a and 2a
enes (2a–d) gave the corresponding products 3a–i in
reasonable yields (61–81%). N-Methanesulfonylimine
of benzaldehyde (1e) showed similar reactivity. Unfortu-
nately, phenyl propargyl ether and 1-decyne, as typical
aliphatic acetylenes, did not undergo the reaction. This
might be due to the low acidity of the acetylenic hydro-
gen in these substrates.8
Entry
1
Conditions
Yield (%)
15
THF, InCl3 (1.2equiv)
Et3N (1.2equiv), 50–60°C, 60h
CH3CN, ZnCl2 (1.2equiv)
Et3N (1.2equiv), 50–60°C, 20h
CH3CN, ZnBr2 (0.2equiv)
DIEA (1.3equiv), 50–60°C, 24h
CH3CN, ZnBr2 (1.2equiv)
Et3N (1equiv), rt, 13h
2
3
4
5
6
7
8
9
10
22
No reaction
In the reaction of 1a and ethyl propiolate (4a) under the
same reaction conditions we could not obtain the corre-
sponding N-tosyl propargylamine product. Instead, we
isolated 3-(N-ethyl-N-isopropyl)aminoacrylic acid ethyl
ester (5a) in 55% yield. The formation of such enamin-
one ester compound has been reported recently.5a,9
As shown in Table 3, we examined the reaction of some
tertiary amines (DIEA, Et3N, N,N-dimethylbenzyl-
amine, DABCO, etc.) and ethyl propiolate (4a) and
methyl propiolate (4b), and ethyl phenylpropiolate
(not shown). The use of DABCO (not shown) and
N,N-dimethylbenzylamine did not show good results.
In the case of ethyl phenylpropiolate the reaction com-
pletely failed. In other cases as shown in Table 3, mod-
erate yields of enaminone esters were obtained. The
plausible reaction mechanism is depicted in Scheme 3.
Michael-type addition of tertiary amine to the activated
propiolate with ZnBr2 would produce zwitterionic spe-
cies. Dissociation of the zwitterion into product oc-
curred presumably via SN1-type mechanism, which
was evidenced by the selective loss of isopropyl moiety
when we used DIEA. This was confirmed once again
for the synthesis of 5c (selective loss of benzyl group
in this case).
62
CH3CN, ZnBr2 (1.2equiv)
Et3N (1.2equiv), 50–60°C, 5h
CH3CN, ZnBr2 (1.2equiv)
DIEA (1.2equiv), 50–60°C, 6h
THF, ZnBr2 (1.2equiv)
78
31
Et3N (1.2equiv), 50–60°C, 15h
Benzene, ZnBr2 (1.2equiv)
DIEA (1.2equiv), 50–60°C, 13h
CH3CN, ZnBr2 (1.2equiv)
DABCO (1.2equiv), 50–60°C, 48h
48
No reaction
to be less effective than acetonitrile (entry 6). Triethyl-
amine was slightly less effective than DIEA (cf. entries
5 and 6). When we used DABCO as the base catalyst,
instant formation of solid materials was observed with
no product formation (entry 9). From the preliminary
investigation we chose the optimal conditions: ZnBr2
(1.2equiv), DIEA (1.2equiv), acetonitrile as solvent,
50–60°C (entry 6).
The plausible mechanism for formation of the zinc acet-
ylide species from the reaction conditions can be
thought as in Scheme 2.4e,6b First, formation of weak
p-complex between the triple bond and Lewis acid
makes the hydrogen of aryl acetylene more acidic. Sub-
sequent deprotonation with amine base generates the
zinc acetylide species, which undergo the next addition
reaction with N-tosylimines.
Synthesized N-tosyl propargylamines could be con-
verted easily into N-cinnamyl tosylamides by partial
reduction of the triple bond with Lindlar catalyst.
Derivatives of N-cinnamyl tosylamides have been used
widely in organic synthesis.10 Thus we examined the
reduction of N-tosylpropargyl amine 3a into 6 with
Lindlar catalyst (Scheme 4). In the reaction, small
amounts of the fully hydrogenated compound 7 was
formed together.
Table 2 shows the representative examples for the syn-
thesis of N-tosyl propargylamines 3. As shown, versatile
combinations of N-sulfonylimines (1a–e) and aryl acetyl-
ZnBr2
NR3
ZnBr
ZnBr
H
H
NR3
π-complex
1a
ZnBr2
3a
2a
Scheme 2.

K. Y. Lee et al. / Tetrahedron Letters 46 (2005) 69–74
Table 2. Synthesis of N-tosylpropargylamines 3a–ia
71
Entry
1
2
Time (h)
Products (%)
Ts
H
N
NTs
1
6
3a (78)
Cl
Cl
N
1a
1a
2a
Ts
H
2
3
4
5
6
7
8
9
6
8
8
8
6
8
8
6
3b (81)
H3C
Cl
N
CH3
2b
Ts
Ts
H
H
1a
1a
3c (67)
F
Cl
N
F
2c
3d (77)
H3CO
Cl
N
OCH3
2d
Ts
H
H
NTs
2a
2a
2a
2a
2b
3e (71)b
1b
Ts
Ts
N
NTs
NTs
3f (72)
H3C
H3C
1c
H
N
3g (61)
Cl
N
N
N
Cl
1d
Ms
Ts
H
H
NMs
3h (69)
1e
1b
N
3i (74)
CH3
a Conditions: sulfonylimine 1 (1.0equiv), aryl acetylene 2 (1.2equiv), DIEA (1.2equiv), ZnBr2 (1.2equiv), CH3CN, 50–60°C, given time.
b 43% yield in Ref. 3.
In order to show the general applicability of the reagents
system we tried the reaction with in situ generated N-
benzoylquinolinium chloride (Scheme 5). As expected
2-phenylethynyl-N-benzoyl dihydroquinoline 8 was ob-
tained in 74% yield.14 Typical experimental procedures
for the synthesis of 3a,11 5a,12 6,13 8,14 and the spectro-
scopic data of prepared compounds are summarized in
the references and notes.
In summary, we disclosed in this paper the synthesis of
N-tosyl propargylamines from the reaction of N-tosyl-
imine and aryl acetylene with the aid of ZnBr2 and

72
K. Y. Lee et al. / Tetrahedron Letters 46 (2005) 69–74
Table 3. Synthesis of enaminone esters 5a–e
ZnBr2 (1 equiv)
CH3CN
50-60 oC, 9-14 h
COOR'
COOR'
R3N
+
R2N
Amine
Propiolate
Time (h)
12
Product
Yield (%)
55a
COOEt
COOEt
5a
5b
N
COOEt
N
4a
4a
N
N
13
14
53
29
COOEt
N
Ph
4a
5c
N
COOMe
COOMe
12
9
5d
5e
61
56
N
N
COOMe
N
N
4b
4b
a The yield was increased to 61% (toluene, reflux, 20h).
H
N
O
ZnBr
O
ZnBr2
H
N
OEt
OEt
4a
Br
SN1 >> SN2
COOEt
N
5a
Scheme 3. Postulated reaction mechanism.
Ts
H
NHTs
NHTs
N
H2, Lindlar catalyst
EtOH/THF, rt, 10 h
Cl
Cl
Cl
7
6
3a
91% (9:1)
Scheme 4.
benzoyl chloride (1.3 equiv)
ZnBr2 (1.2 equiv)
N
+
DIEA (1.2 equiv)
CH3CN, rt, 20 min
N
Ph
O
Ph
8
Scheme 5.

K. Y. Lee et al. / Tetrahedron Letters 46 (2005) 69–74
73
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DIEA in CH3CN. During the investigation we could
widen the scope and understanding of the newly devel-
oping concept of acid–base combination for the intro-
duction of acetylenic compounds onto electrophiles.
6. For the enantioselective alkynylation of aldehydes or
aldimines, see: (a) Wei, C.; Li, C.-J. J. Am. Chem. Soc.
2002, 124, 5638; (b) Dahmen, S. Org. Lett. 2004, 6, 2113;
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(a) Lee, K. Y.; Lee, C. G.; Kim, J. N. Tetrahedron Lett.
2003, 44, 1231; (b) Kim, J. N.; Lee, H. J.; Lee, K. Y.;
Gong, J. H. Synlett 2002, 173; (c) Kim, J. N.; Lee, H. J.;
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1999, 40, 4363.
Acknowledgements
This work was supported by the grant (R05-2003-000-
10042-0) from the Basic Research Program of the Korea
Science & Engineering Foundation. Spectroscopic data
was obtained from the Korea Basic Science Institute,
Kwangju branch.
References and notes
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Campi, E. M.; Jackson, W. R.; Nilsson, Y. Tetrahedron
Lett. 1991, 32, 1093; (i) Mandai, T.; Ryoden, K.; Kawada,
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1986, 108, 6053; (l) Clive, D. L. J.; Cole, D. C.; Tao, Y. J.
Org. Chem. 1994, 59, 1396; (m) Yu, P. H.; Davis, B. A.;
Boulton, A. A. J. Med. Chem. 1992, 35, 3705.
2. For the alkynylation reaction using acetylide, which was
generated by the action of strong base including n-BuLi,
EtMgBr, benzyltrimethylammonium hydroxide, or cesium
hydroxide, see: (a) Murai, T.; Mutoh, Y.; Ohta, Y.;
Murakami, M. J. Am. Chem. Soc. 2004, 126, 5968; (b)
Tzalis, D.; Knochel, P. Angew. Chem., Int. Ed. 1999, 38,
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3. Frantz, D. E.; Fassler, R.; Carreira, E. M. J. Am. Chem.
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nation concept, see: (a) Sakai, N.; Hirasawa, M.; Konaka-
hara, T. Tetrahedron Lett. 2003, 44, 4171; (b) Jiang, B.; Si,
Y.-G. Tetrahedron Lett. 2002, 43, 8323; (c) Jiang, B.; Si,
Y.-G. Tetrahedron Lett. 2003, 44, 6767; (d) Knopfel, T. F.;
Boyall, D.; Carreira, E. M. Org. Lett. 2004, 6, 2281; (e)
Black, D. A.; Arndtsen, B. A. Org. Lett. 2004, 6, 1107; (f)
Han, Y.; Huang, Y.-Z. Tetrahedron Lett. 1995, 36, 7277;
(g) Yamaguchi, M.; Hayashi, A.; Minami, T. J. Org.
Chem. 1991, 56, 4091.
5. For the related alkynylation reaction using similar
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Int. Ed. 2004, 43, 2525; (b) Wei, C.; Li, C.-J. J. Am. Chem.
Soc. 2003, 125, 9584; (c) Wei, C.; Li, Z.; Li, C.-J. Org.
Lett. 2003, 5, 4473; (d) Knopfel, T. F.; Carreira, E. M. J.
Am. Chem. Soc. 2003, 125, 6054; (e) Tejedor, D.; Gonz-
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Lett. 2004, 6, 2333; (g) Chen, L.; Li, C.-J. Tetrahedron
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Tetrahedron Lett. 2002, 43, 5731; (i) Auge, J.; Lubin-
8. Lee, K. Y.; Lee, M. J.; GowriSankar, S.; Kim, J. N.
Tetrahedron Lett. 2004, 45, 5043.
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esters, see: (a) Gurtler, C. F.; Steckhan, E.; Blechert, S. J.
Org. Chem. 1996, 61, 4136; (b) Barton, D. H. R.; Langlois,
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11. Typical procedure for the synthesis of 3a: To a stirred
solution of 1a (294mg, 1.0mmol) in CH3CN (3mL) was
added phenylacetylene (2a, 123mg, 1.2mmol), ZnBr2
(270mg, 1.2mmol), and N,N-diisopropylethylamine
(DIEA, 155mg, 1.2mmol). The reaction mixture was
stirred for 6h at 50–60°C. After the usual aqueous workup
and column chromatographic purification process (hex-
anes/ether, 10:1) we obtained 3a as a white solid, 309mg
(78%). The spectroscopic data of prepared compounds are
as follows. 3a: mp 188–189°C; 1H NMR (300MHz,
CDCl3) d 2.31 (s, 3H), 5.12 (d, J = 8.4Hz, 1H), 5.83 (d,
J = 8.4Hz, 1H), 7.14–7.30 (m, 10H), 7.53–7.58 (m, 1H),
7.78 (d, J = 8.4Hz, 2H); 13C NMR (75MHz, CDCl3) d
21.65, 48.24, 85.19, 86.57, 122.13, 127.44, 127.71, 128.33,
128.86, 129.60, 129.70, 130.06, 130.43, 131.84, 133.32,
135.35, 137.48, 143.76; Mass (70eV) m/z (rel. intensity) 91
(100), 105 (64), 139 (41), 240 (M+ À SO2Tol, 72), 395 (M+,
0.4). 3b: mp 127–128°C; 1H NMR (300MHz, CDCl3) d
2.30 (s, 3H), 2.31 (s, 3H), 5.36 (d, J = 8.4Hz, 1H), 5.82 (d,
J = 8.4Hz, 1H), 7.03 (s, 4H), 7.15–7.25 (m, 4H), 7.28–7.33
(m, 1H), 7.54–7.57 (m, 1H), 7.76 (d, J = 8.4Hz, 2H); 13C
NMR (75MHz, CDCl3) d 21.59, 21.63, 48.08, 84.53,
86.65, 119.02, 127.38, 127.64, 129.01, 129.56, 129.62,
129.90, 130.24, 131.70, 133.19, 135.49, 137.45, 138.94,
143.61. 3c: mp 126–127°C; 1H NMR (300MHz, CDCl3) d

74
K. Y. Lee et al. / Tetrahedron Letters 46 (2005) 69–74
2.32 (s, 3H), 5.16 (d, J = 9.0Hz, 1H), 5.53 (d, J = 9.0Hz,
as clear oil, 102mg (55%). The spectroscopic data of
prepared compounds are as follows. For 5b and 5c we
could not obtain the exact 13C NMR spectra due to the
line broadening effect of nitrogen atom.
1H), 6.90–6.96 (m, 2H), 7.07–7.12 (m, 2H), 7.20 (d,
J = 8.1Hz, 2H), 7.29–7.35 (m, 3H), 7.50–7.53 (m, 2H),
7.80 (d, J = 8.4Hz, 2H); 13C NMR (75MHz, CDCl3) d
21.60, 49.90, 85.51 (d, J = 1.4Hz), 85.74, 115.58 (d,
J = 21.8Hz), 118.27 (d, J = 3.8Hz), 127.48, 127.72,
128.66, 128.91, 129.70, 133.69 (d, J = 8.3Hz), 137.57 (d,
J = 6.3Hz), 143.66, 161.10, 164.42. 3d: mp 122–123°C; 1H
NMR (300MHz, CDCl3) d 2.29 (s, 3H), 3.75 (s, 3H), 5.30
(d, J = 9.3Hz, 1H), 5.51 (d, J = 9.3Hz, 1H), 6.74 (d,
J = 8.7Hz, 2H), 7.03 (d, J = 8.7Hz, 2H), 7.17 (d,
J = 8.1Hz, 2H), 7.20–7.33 (m, 3H), 7.49–7.53 (m, 2H),
7.76 (d, J = 8.4Hz, 2H); 13C NMR (75MHz, CDCl3)
d21.72, 50.11, 55.57, 84.49, 86.89, 114.02, 114.39, 127.63,
127.80, 128.60, 128.92, 129.79, 133.33, 137.74, 138.03,
143.67, 160.01. 3e: mp 187–188°C;1 H NMR (300MHz,
CDCl3) d 2.31 (s, 3H), 4.96 (d, J = 9.3Hz, 1H), 5.56 (d,
J = 9.3Hz, 1H), 7.10–7.14 (m, 2H), 7.21–7.38 (m, 8H),
7.53–7.57 (m, 2H), 7.81 (d, J = 8.4Hz, 2H); 13C NMR
(75MHz, CDCl3) d 21.40, 49.77, 85.46, 86.68, 121.95,
127.32, 127.52, 128.09, 128.46, 128.57, 128.70, 129.55,
131.55, 137.37, 137.39, 143.55; Mass (70eV) m/z (rel.
intensity) 65 (60), 77 (71), 91 (100), 105 (51), 128 (46), 191
(34), 206 (M+ À SO2Tol, 90). 3f: mp 194–195°C; 1H NMR
(300MHz, CDCl3) d 2.31 (s, 3H), 2.34 (s, 3H), 4.91 (d,
J = 9.0Hz, 1H), 5.52 (d, J = 9.0Hz, 1H), 7.09–7.29 (m,
1
5a: oil; H NMR (300MHz, CDCl3) d 1.15 (t, J = 7.2Hz,
3H), 1.21 (d, J = 6.6Hz, 6H), 1.26 (t, J = 7.2Hz, 3H) 3.14
(q, J = 7.2Hz, 2H), 3.52 (septet, J = 6.6Hz, 1H), 4.13 (q,
J = 7.2Hz, 2H), 4.58 (d, J = 13.2Hz, 1H), 7.51 (d,
J = 13.2Hz, 1H); 13C NMR (75MHz, CDCl3) d 12.91,
14.80, 21.70, 41.01, 56.01, 58.84, 83.35, 149.46, 170.17. 5b:
oil; 1H NMR (300MHz, CDCl3) d 1.16 (t, J = 7.2Hz, 6H),
1.26 (t, J = 7.2Hz, 3H), 3.19 (q, J = 7.2Hz, 4H), 4.13 (q,
J = 7.2Hz, 2H), 4.57 (d, J = 12.9Hz, 1H), 7.44 (d,
J = 12.9Hz, 1H); 13C NMR (75MHz, CDCl3) d 14.66,
1
58.79, 83.37, 150.89, 170.00. 5c: oil; H NMR (300MHz,
CDCl3) d 1.26 (t, J = 7.2Hz, 3H), 2.88 (s, 6H), 4.13 (q,
J = 7.2Hz, 2H), 4.52 (d, J = 12.9Hz, 1H), 7.44 (d,
J = 12.9Hz, 1H). 5d: oil; IR (neat) 3498, 2974, 1689,
; d 1.15 (t,
1608cmÀ1 1H NMR (300MHz, CDCl3)
J = 7.2Hz, 3H), 1.21 (d, J = 6.9Hz, 6H), 3.14 (q,
J = 7.2Hz, 2H), 3.52 (septet, J = 6.9Hz, 1H), 3.66 (s,
3H), 4.58 (d, J = 13.2Hz, 1H), 7.51 (d, J = 13.2Hz, 1H);
13C NMR (75MHz, CDCl3) d 12.96, 21.71, 41.09, 50.49,
55.91, 83.00, 149.53, 170.52; Mass (70eV) m/z (rel.
intensity) 41 (100), 56 (97), 70 (72), 140 (56), 156 (49),
171 (M+, 22). 5e: oil; IR (neat) 3510, 2978, 1689,
9H), 7.42 (d, J = 8.4Hz, 2H), 7.81 (d, J = 8.4Hz, 2H); 13
C
1612cmÀ1 1H NMR (300MHz, CDCl3)
; d 1.16 (t,
NMR (75MHz, CDCl3) d 21.37, 21.68, 49.82, 85.97,
86.75, 122.32, 127.51, 127.81, 128.35, 128.79, 129.64,
129.80, 131.82, 134.76, 137.71, 138.61, 143.77. 3g: mp
224–225°C; 1H NMR (300MHz, CDCl3 + DMSO-d6) d
2.21 (s, 3H), 5.83 (s, 1H), 7.15–7.38 (m, 7H), 7.68– 7.74 (m,
3H), 7.86 (t, J = 8.4Hz, 1H), 7.98 (d, J = 8.7Hz, 1H), 8.09
(d, J = 7.8Hz, 1H), 8.59 (s, 1H), 8.91 (br s, 1H); 13C NMR
(75MHz, CDCl3 + DMSO-d6) d 19.15, 44.88, 83.35, 84.02,
119.55, 124.98, 125.11, 125.84, 125.89, 126.52, 126.65,
127.18, 127.64, 127.98, 129.52, 129.70, 136.25, 136.37,
141.12, 144.80, 146.61. 3h: oil; 1H NMR (300MHz,
CDCl3) d 3.08 (s, 3H), 4.96 (d, J = 8.1Hz, 1H), 5.64 (d,
J = 7.2Hz, 6H), 3.19 (q, J = 7.2Hz, 4H), 3.65 (s, 3H),
4.56 (d, J = 12.9Hz, 1H), 7.44 (d,J = 12.9Hz, 1H); 13C
NMR (75MHz, CDCl3) d 13.01, 43.31, 50.37, 83.03,
150.98, 170.31; Mass (70eV) m/z (rel. intensity) 41 (67), 55
(100), 98 (37), 126 (53), 142 (27), 157 (M+, 26).
13. Spectroscopic data of partial reduction product 6: 1H
NMR (300MHz, CDCl3)
d 2.35 (s, 3H), 5.07 (d,
J = 5.4Hz, 1H), 5.61 (dd, J = 9.3 and 5.4Hz, 1H), 5.87
(dd, J = 11.4 and 9.3Hz, 1H), 6.57 (d, J = 11.4Hz, 1H),
7.05–7.33 (m, 11H), 7.49 (d, J = 8.4Hz, 2H); Mass (70eV)
m/z (rel. intensity) 91 (100), 138 (30), 242 (41), 397 (M+, 2).
14. To a stirred solution of quinoline (130mg, 1mmol) in
CH3CN (2mL) was added benzoyl chloride (183mg,
1.3mmol), phenylacetylene (122mg, 1.2mmol), ZnBr2
(270mg, 1.2mmol), and N,N-diisopropylethylamine
(155mg, 1.2mmol) successively at room temperature.
After 20min the reaction mixture was poured into cold
water. After normal workup with ether, removal of
solvent, flash column chromatographic purification (hex-
anes/ether, 40:1) we obtained the desired dihydroquinoline
J = 8.1Hz, 1H), 7.30–7.49 (m, 8H), 7.60–7.64 (m, 2H); 13
C
NMR (75MHz, CDCl3) d 41.78, 49.80, 86.04, 86.98,
121.78, 127.42, 128.47, 128.73, 128.90, 129.00, 131.67,
1
137.27. 3i: mp 145–146°C; H NMR (300MHz, CDCl3) d
2.33 (s, 6H), 4.94 (d, J = 7.8Hz, 1H), 5.54 (d, J = 7.8Hz,
1H), 6.99–7.07 (m, 4H), 7.23 (d, J = 8.7Hz, 2H), 7.30–7.37
(m, 3H), 7.53–7.57 (m, 2H), 7.81 (d, J = 8.4Hz, 2H); 13C
NMR (75MHz, CDCl3) d 21.65, 21.66, 50.03, 85.01,
87.05, 119.10, 127.56, 127.75, 128.63, 128.89, 129.06,
129.76, 131.68, 137.63, 137.77, 138.97, 143.70.
8, 248mg (74%): IR (KBr) 2218, 1651cmÀ1 1H NMR
;
(300MHz, CDCl3) d 6.19–6.24 (m, 2H), 6.65–6.70 (m,
2H), 6.90 (t, J = 7.5Hz, 1H), 7.05 (td, J = 7.5 and 1.2Hz,
1H), 7.17–7.45 (m, 11H); 13C NMR (75MHz, CDCl3) d
44.42, 83.66, 85.07, 122.38, 125.10, 125.61, 125.71, 126.13,
126.53, 126.84, 127.12, 127.98, 128.06, 128.25, 128.98,
130.58, 131.79, 134.94, 135.15, 169.38; Mass (70eV) m/z
(rel. intensity) 77 (52), 105 (100), 129 (18), 230 (14), 306
(13), 335 (M+, 7).
12. Typical procedure for the synthesis of enaminone ester 5a:
To s stirred solution of ethyl propiolate (98mg, 1.0mmol)
in CH3CN (3mL) was added ZnBr2 (225mg, 1.0mmol)
and N,N-diisopropylethylamine (130mg, 1.0mmol). The
reaction mixture was stirred for 12h at 50–60°C. After the
usual aqueous workup and column chromatographic
purification process (hexanes/ether, 5:1) we obtained 5a