S. Gupta et al. / Tetrahedron Letters 52 (2011) 5752–5757
5757
6024; (b) Sharma, S. K.; Gupta, S.; Saifuddin, M.; Mandadapu, A. K.; Agarwal, P.
K.; Gauniyal, H. M.; Kundu, B. Tetrahedron Lett. 2011, 52, 65–68; (c) Saifuddin,
M.; Agarwal, P. K.; Sharma, S.; Mandadapu, A. K.; Gupta, S.; Harit, V. K. Eur. J.
Org. Chem. 2010, 26, 5108–5117; (d) Agarwal, P. K.; Sawant, D.; Sharma, S.;
Kundu, B. Eur. J. Org. Chem. 2009, 2, 292–303; (e) Sharma, S. K.; Sharma, S.;
Agarwal, P. K.; Kundu, B. Eur. J. Org. Chem. 2009, 9, 1309–1312; (f) Saha, B.;
Sharma, S.; Sawant, D.; Kundu, B. Tetrahedron Lett. 2007, 48, 1379–1383; (g)
Sawant, D.; Kumar, R.; Maulik, P. R.; Kundu, B. Org. Lett. 2006, 8, 1525–1528.
10. (a) Pathak, A.; Singh, S. K.; Biabani, M. A. F.; Srivastava, S.; Kulshreshtha, D. K.;
Puri, S. K.; Kundu, B. Comb. Chem. High Throughput Screening 2002, 5, 241–248;
(b) Srinivasan, T.; Srivastava, G. K.; Pathak, A.; Batra, S.; Puri, S. K.; Raj, K.;
Kundu, B. Bioorg. Med. Chem. Lett. 2002, 12, 2803–2806.
11. Li, D.; Yin, K.; Li, J.; Jia, X. Tetrahedron Lett. 2008, 49, 5918–5919.
12. For review see: Müller, T. E.; Hultzsch, K. C.; Yus, M.; Foubelo, F.; Tada, M.
Chem. Rev. 2008, 108, 3795–3892.
13. Casitas, A.; King, A. E.; Parella, T.; Costas, M.; Stahl, S. S.; Ribas, X. Chem. Sci.
2010, 1, 326–330.
14. To a stirred solution of indole (1.0 mmol)/Imidazole (1.2 mmol) in DMSO was
added 1,3-diyne (1.0 mmol), CuI (0.1 mmol), 1,10-phenanthroline (0.05 mmol)
and cesium carbonate (1.5 mmol). The reaction mixture was heated at 100 °C
for 5–16 h and the completion of the reaction was monitored by TLC. After
completion of the reaction, it was cooled down to room temperature and then
diluted with H2O (5 mL) followed by extraction of the product with EtOAc
(3 Â 10 mL). The combined organic layer was washed with brine, dried over
anhydrous Na2SO4 and the solvent was removed in vacuo. The crude product
was purified on a silica gel column using hexane: ethyl acetate as eluent. The Z
isomer was crytalised using DCM/EtOH in indole and EtOH in case of imidazole.
1-[(Z)-1,4-Diphenylbut-1-en-3-ynyl]-1H-indole (3a).
4 which were obtained as a mixture of Z/E isomers, N-alkenynes 5
derived from acyclic amides were obtained as a single isomer only.
The stereochemistry of the pure isomer so obtained was estab-
lished as E-isomer using 1H, 2D NMR, and NOE studies. Thus
whereas N-heterocycles and cyclic amides produced mixture of
Z/E isomers with high order of Z-stereoselectivity, acyclic amides
exclusively afforded stereoselective E-isomer albeit in lower yields.
The hydro-amination/-amidation followed the order of reactivity
of the NH-substrates with 1,3-diynes: N-heterocycles > cyclic
amides > acyclic amides.
In conclusion, an efficient method for the regio- and stereo-
selective synthesis of N-alkenynes via hydro-amination/amidation
of 1,3-diynes with N-heterocycles, cyclic amides, and acyclic
amides has been developed. The salient feature of our methodol-
ogy involves high order of Z-stereoselectivity among N-alkenynes
(3 and 4) furnished by N-heterocycles and cyclic amides. In con-
trast, hydroamidation of 1,3-diynes with acyclic amides furnished
stereoselective formation of N-alkenynes (5) as E-isomer only.
Nevertheless, the yields of N-alkenynes obtained from N-heterocy-
cles and cyclic amides were significantly higher than afforded by
acyclic amides. Further studies are in progress to use the N-alkeny-
nes intermediates for further synthetic manipulation.
Yield = 0.60 g (58%); white solid; mp 172–174 °C; Rf = 0.31 (hexane); IR (KBr)
mmax 3033, 1586, 1211, 740 cmÀ1 1H NMR (300 MHz, CDCl3) d = 7.67 (1H, d,
;
J = 7.7 Hz, ArH), 7.43 (1H, d, J = 3.2 Hz, ArH), 7.37–7.29 (5H, m, ArH), 7.22–7.04
(7H, m, ArH), 6.96 (1H, d, J = 8.1 Hz, ArH), 6.69 (1H, d, J = 2.9 Hz, ArH), 6.22 (1H,
s, @CH); 13C NMR (75 MHz, CDCl3) d = 146.8, 136.8, 136.2, 131.5, 129.8, 129.4,
129.2, 128.9, 128.4, 128.3, 126.9, 123.2, 122.0, 120.9, 120.4, 112.9, 103.6, 102.6,
97.1, 86.7 ppm; Exact Mass: 284.1313; HR-MS (ESI) found 285.1504 [M+ H]+.
1-[(Z)-1,4-Diphenylbut-1-en-3-ynyl]-2-methyl-1H-imidazole (3m).
Acknowledgments
The authors are grateful to SAIF, CDRI, Lucknow for the spectral
data. S.G., P.K.A., and M.S., are thankful to CSIR, New Delhi, India for
fellowships. BK is thankful to DST, New Delhi, India for the finan-
cial support (VI-D&P/332/09-10/TDT).
Yield = 0.50 g (82%); white solid; mp 76–78 °C; Rf = 0.48 (1:4 EtOAc/hexane); IR
(KBr) mmax 3076, 3035, 1485, 1182 cmÀ1 1H NMR (300 MHz, CDCl3) d = 7.39–
;
7.34 (3H, m, ArH), 7.28–7.26 (5H, m, ArH), 7.23–7.20 (2H, m, ArH), 7.12 (1H, s,
ArH), 6.99 (1H, s, ArH), 6.46 (1H, s, @CH), 2.28 (3H, s, CH3); 13C NMR (75 MHz,
CDCl3) d = 145.7, 144.9, 135.5, 131.8, 130.0, 129.1, 129.0, 128.5, 127.8, 125.5,
122.5, 120.5, 106.7, 98.3, 85.0, 13.5 ppm; Exact Mass: 319.1361; HR-MS (ESI)
found 320.1459 [M+H]+.
Supplementary data
1-[(Z)-1,4-Bis(4-methylphenyl)but-1-en-3-ynyl]-3,5-dimethyl-1H-pyrazole (3v).
Yield = 0.09 g (67%); yellow oil; Rf = 0.65 (1:4 EtOAc/hexane); IR (KBr) mmax
Supplementary data associated with this article can be found, in
3021, 2928, 2194, 1217, 768 cmÀ1 1H NMR (300 MHz, CDCl3) d = 7.17–7.12
;
(4H, m, ArH), 7.08–7.06 (4H, m, ArH), 6.40 (1H, s, ArH), 6.00 (1H, s, @CH), 2.34
(3H, s, CH3), 2.32 (3H, s, CH3), 2.31 (3H, s, CH3), 2.24 (3H, s, CH3); 13C NMR
(50 MHz, CDCl3) d = 149.5, 146.5, 141.9, 139.7, 138.7, 133.6, 131.5, 129.6,
129.1, 125.8, 120.2, 105.8, 105.4, 96.9, 85.5, 21.6, 21.4, 13.9, 11.5 ppm; Exact
Mass: 326.1783; HR-MS (ESI) found 327.1853 [M+H]+.
References and notes
1. (a) Faulkner, D. J. Nat. Prod. Rep. 2001, 18, 1–49. and references cited therein;
(b) Frank, R. Curr. Opin. Biotechnol. 2004, 15, 573–575. and references cited
therein; (c) Kumar, K.; Waldmann, H. Angew. Chem., Int. Ed. 2009, 48, 3224–
3242; (d) Bennasar, M. L.; Vidal, B.; Bosch, J. J. Org. Chem. 1997, 62, 3597–3609;
(e) Zhang, H. C.; Ye, H.; Moretto, A. F.; Brumeld, K. K.; Maryano, B. E. Org. Lett.
2000, 2, 89–92; (f) Marugan, J. J.; Manthey, C.; Anaclerio, B.; Lafrance, L.; Lu, T.;
Markotan, T.; Leonard, K. A.; Crysler, C.; Eisennagel, S.; Dasgupta, M.; Tomczuk,
B. J. Med. Chem. 2005, 48, 926–934; (g) Faul, M. M.; Winneroski, L. L.; Krumrich,
C. A. J. Org. Chem. 1998, 63, 6053–6058; (h) Horton, D. A.; Bourne, G. T.; Smythe,
M. L. Chem. Rev. 2003, 103, 893–930.
1-[(Z)-1-(4-methoxyphenyl)-4-phenylbut-1-en-3-ynyl]pyrrolidin-2-one (4c).
Yield = 0.065 g (50%); off white solid; mp = 187–189 °C; Rf = 0.21 (3:7 EtOAc/
hexane); IR (KBr) m ;
max 2958, 1691, 1250, 770 cmÀ1 1H NMR (300 MHz, CDCl3)
d = 7.37–7.32 (4H, m, ArH), 6.90–6.83 (4H, m, ArH), 6.12 (1H, s, CH), 3.82 (3H, s,
OCH3), 3.81 (3H, s, OCH3), 3.75 (2H, t, J = 6.9 Hz, CH2), 2.59 (2H, t, J = 6.9 Hz,
CH2), 2.28 (2H, m, CH2); 13C NMR (50 MHz, CDCl3) d = 174.4, 160.6, 159.8,
145.3, 132.9, 127.6, 127.0, 115.5, 114.3, 114.1, 104.0, 97.2, 85.1, 55.4, 55.3, 49.0,
31.6, 19.6 ppm; Exact Mass: 347.1521; HR-MS (ESI) found 348.1602 [M+H]+.
N-[(E)-1,4-Diphenylbut-1-en-3-ynyl]-4-methoxy-N-(4-methylbenzyl)-
benzamide (5a). Yield = 0.050 g (22%); yellow oil; Rf = 0.58 (1:4 EtOAc/hexane);
2. Balón, M.; Carmona, M. C.; Muñoz, M. A.; Hidalgo, J. Tetrahedron 1989, 45,
7501–7504.
IR (KBr) mmax 3029, 2927, 2166, 1726, 1219, 771 cmÀ1 1H NMR (300 MHz,
;
3. Bellina, F.; Benelli, F.; Rossi, R. J. Org. Chem. 2008, 73, 5529–5535.
4. (a) Verma, A. K.; Joshi, M.; Singh, V. P. Org. Lett. 2011, 13, 1630–1633; (b) Hong,
S.; Marks, T. J. Acc. Chem. Res. 2004, 37, 673–686; (c) Pohlki, F.; Doye, S. Chem.
Soc. Rev. 2003, 32, 104–114; (d) Shanbhag, G. V.; Palraj, K.; Halligudi, S. B.
The.Open.Organic.Chemistry Journal 2008, 2, 52–57; (e) Severin, R.; Doye, S.
Chem. Soc. Rev. 2007, 36, 1407–1420; (f) Wang, M.; Wu, J.; Shang, Z. J. Org.
Chem. 2011, dx.doi.org./10.1021/jo2004346.
5. Siddle, J. S.; Batsanov, A. S.; Bryce, M. R. Eur. J. Org. Chem. 2008, 16, 2746–2750.
6. Ullmann, F.; Bielecki, J. Ber. Dtsch. Chem. Ges. 1901, 34, 2174–2185.
7. For recent review: (a) Evano, G.; Blanchard, N.; Toumi, M. Chem. Rev. 2008, 108,
3054–3131; (b) Ley, S. V.; Thomas, A. W. Angew. Chem., Int. Ed. 2003, 42, 5400–
5449; (c) Tasler, S.; Mies, J.; Langa, M. Adv. Synth. Catal. 2007, 349, 2286–2300;
(d) Chen, Y.; Chen, H. Org. Lett. 2006, 8, 5609–5612; (e) Altman, R. A.; Shafir, A.;
Choi, A.; Lichtor, P. A.; Buchwald, S. L. J. Org. Chem. 2008, 73, 284–286.
8. Alves, D.; Sachini, M.; Jacob, R. G.; Lenardao, E. J.; Contreira, M. E.; Savegnago,
L.; Perin, G. Tetrahedron Lett. 2011, 52, 133–135.
CDCl3) d = 7.57–7.54 (2H, m, ArH), 7.51–7.48 (2H, m, ArH), 7.42–7.37 (3H, m,
ArH), 7.33–7.28 (5H, m, ArH), 7.25–7.24 (2H, m, ArH), 6.96 (2H, d, J = 7.8 Hz,
ArH), 6.65 (2H, d, J = 8.8 Hz, ArH), 5.82 (1H, s, @CH); 5.45 (1H, d, J = 13.7 Hz,
CH), 4.29 (1H, d, J = 13.7 Hz, CH), 3.72 (3H, s, OCH3), 2.20 (3H, s, CH3); 13C NMR
(50 MHz, CDCl3) d = 171.3, 161.3, 149.8, 137.1, 135.8, 133.8, 131.5, 130.0,
129.6, 129.2, 128.7, 128.4, 126.8, 123.2, 113.4, 112.8, 106.8, 96.8, 87.2, 55.3,
50.5, 21.2 ppm; Exact Mass: 457.2042; HR-MS (ESI) found 458.2167 [M+H]+.
N-[(E)-1,4-Bis(4-methylphenyl)but-1-en-3-ynyl]-N-(4-chlorophenyl) acetamide
(5f). Yield = 0.072 g (40%); yellow oil; Rf = 0.62 (1:4 EtOAc/hexane); IR (KBr)
mmax 2924, 2193, 1637, 1220 cmÀ1 1H NMR (300 MHz, CDCl3) d = 7.41–7.36
;
(4H, m, ArH), 7.29 (2H, d, J = 8.1 Hz, ArH), 7.23 (2H, d, J = 8.7 Hz, ArH), 7.16 (2H,
d, J = 8.0 Hz, ArH), 7.11 (2H, d, J = 8.0 Hz, ArH), 6.44 (1H, s, @CH), 2.34 (6H, s,
2 Â CH3), 2.32 (3H, s, CH3); 13C NMR (75 MHz, CDCl3) d = 171.2, 148.8, 140.2,
139.4, 138.9, 132.4, 131.7, 129.9, 129.3, 128.9, 127.1, 125.8, 119.5, 108.2, 98.3,
85.4, 23.1, 21.6, 21.3 ppm; Exact Mass: 399.1390; HR-MS (ESI) found 400.1476
[M+H]+.
9. (a) Sharma, S. K.; Mandadapu, A. K.; Saifuddin, M.; Gupta, S.; Agarwal, P. K.;
Mandwal, A. K.; Gauniyal, H. M.; Kundu, B. Tetrahedron Lett. 2010, 51, 6022–