chemists to pursue the synthesis of numerous imidazopyr-
idine derivatives6 and study their properties.7 Synthetic
approaches include reaction of aminopyridines with
R-functionalized and R,β-unsaturated carbonyl com-
pounds, 1,3-dicarbonyl compounds, vicinal diols as well
as with simple aldehydes and ketones, often in a multi-
component reaction.8ꢀ10 Reactions involving Sandmeyer
conditions, rearrangement, cycloaddition, Michael addi-
tion and other miscellaneous ones were also employed for
the synthesis of imidazopyridines.11ꢀ13
From another perspective, the MoritaꢀBaylisꢀHillman
(MBH) reaction has emerged in recent decades as one of
the most sought after reactions for the synthesis of various
multifunctional scaffolds.14 The MBH acetatesof electron-
deficient alkenes have been subjected to substitution,
often SN20, by numerous nucleophiles including amines
under uncatalyzed, organocatalyzed and metal-catalyzed
conditions.14ꢀ16 However, to our knowledge, synthesis of
imidazopyridines from the MBH adducts of electron-deficient
alkenes, including nitroalkenes, remains unreported.17
Recently, Chen et al. and we have independently re-
ported the synthesis of fused and functionalized furans and
pyrans through the reaction of MBH acetates of nitroalk-
enes 1 with β-dicarbonyl compounds 2 thus demonstrating
for the first time the potential of 1 to undergo multiple
nucleophilic additions in a cascade fashion (Scheme 1,
path a).18 We realized that imidazopyridines 6 and/or
pyrimidopyridines 7 with a strategically positioned ester
group would be accessible if 2-aminopyridine 5a and
similar nucleophiles react with MBH acetates 1 in a
cascade inter-intramolecular double Michael reaction
(Scheme 1, path b).
(7) Review on the physical and chemical properties as well as reac-
tions of 2,3-dihydroimidazo[1,2-a]pyridines: (a) Sulojeva, E.; Yure, M.;
Gudriniece, E. Chem. Heterocycl. Compd. 2001, 36, 885. For an article:
(b) Pericherla, K.; Khungar, B.; Kumar, A. Tetrahedron Lett. 2012, 53,
1253.
(8) With R-halocarbonyl compounds, recent articles: (a) El Kazzouli,
S.; Berteina-Raboin, S.; Mouaddib, A.; Guillaumet, G. Lett. Org. Chem.
2012, 9, 118. (b) Adib, M.; Mohamadi, A.; Sheikhi, E.; Ansari, S.;
Bijanzadeh, H. R. Synlett 2010, 1606. (c) Patil, S. S.; Patil, S. V.; Bobade,
V. D. Org. Prep. Proced. Int. 2011, 43, 260. (d) Chunavala, K. C.; Joshi,
G.; Suresh, E.; Adimurthy, S. Synthesis 2011, 4, 635. (e) Sumalatha, Y.;
Reddy, T. R.; Reddy, P. P.; Satyanarayana, B. ARKIVOC 2009, ii, 315.
(f) See refs 4b, 4d, 4f, 5a, 5b, and the Supporting Information.
(9) With R-diazocarbonyl compounds: (a) Yadav, J. S.; Reddy,
B. V. S.; Rao, Y. G.; Srinivas, M.; Narsaiah, A. V. Tetrahedron Lett.
2007, 48, 7717. With R-organosulfonyloxy ketones: (b) Huang, H. Y.;
Hou, R. S.; Wang, H. M.; Chen, L. C. J. Chin. Chem. Soc. 2004, 51, 1377.
With R,β-unsaturated aldehydes and ketones: (c) Jones, R. C. F.;
Dimopoulos, P.; Coles, S. C.; Light, M. E.; Hursthouse, M. B. J. Chem.
Soc., Perkin Trans. 1 2000, 15, 2331. With 1,3-dicarbonyl compounds:
(d) Ma, L.; Wang, X.; Yu, W.; Han, B. Chem. Commun. 2011, 47, 11333.
With vicinal diols: (e) Kondo, T.; Kotachi, S.; Ogino, S.; Watanabe, Y.
Chem. Lett. 1993, 8, 1317. With arylketones: (f) Stasyuk, A. J.;
Banasiewicz, M.; Cyranski, M. K.; Gryko, D. T. J. Org. Chem. 2012,
77, 5552. (g) Chang, Y. L.; Wang, H. M.; Hou, R. S.; Kang, I. J.; Chen,
L. C. J. Chin. Chem. Soc. 2010, 57, 153. With methylene ketones
(h) Saldaboln, N.; Hillers, S. Khim. Geterotsikl. Soedin. 1976, 10, 1396
and see also the Supporting Information.
Scheme 1. MBH Adducts of Nitroalkenes 1 as Novel Synthetic
Scaffolds
(10) With aldehydes and terminal alkynes: (a) Mishra, S.; Ghosh, R.
Synthesis 2011, 21, 3463. (b) Reddy, S. B. V.; Reddy, S. P.; Reddy, J. Y.;
Yadav, J. S. Tetrahedron Lett. 2011, 52, 5789. (c) Chernyak, N.;
Gevorgyan, V. Angew. Chem., Int. Ed. 2010, 49, 2743. With aromatic
aldehyde and TMSCN: (d) Venkatesham, R.; Manjula, A.; Rao, B. V.
J. Heterocyclic Chem. 2011, 48, 942. With aldehydes and isocyanides:
(e) Adib, M.; Sheikhi, E.; Rezaei, N. Tetrahedron Lett. 2011, 52, 3191.
(f) Khan, A. T.; Basha, R. S.; Lal, M. Tetrahedron Lett. 2012, 53, 2211.
(g) See ref 4e and the Supporting Information.
(11) Via Sandmeyer reaction: (a) Sucunza, D.; Samadi, A.; Chioua,
M.; Silva, D. B.; Yunta, C.; Infantes, L.; Carmo, C. M.; Soriano, E.;
Marco-Contelles, J. Chem. Commun. 2011, 47, 5043. Via rearrangement
of2-pyridyl-3-(arylamino)isoxazol-5(2H)-ones:(b)Khalafy, J.;Ebrahimlo,
A. R. M.; Eisavi, R.; Dilmaghani, K. A. ARKIVOC 2005, 14, 59.
(c) Khalafy, J.; Setamdideh, D.; Dilmaghani, K. A. Molecules 2002, 7,
907. Via Cycloaddition of isonitrosoflavanone esters with schiff Bases:
(d) Katritzky, A. R.; Michalska, M. J. Chem. Soc., Perkin Trans. I 1980,
354. For synthesis of nitroimidazopyridines via Michael addition of
aminopyridine to nitroalkene and subsequent Cu(I) catalyzed intramole-
cular cyclization: (e) Yan, R. L.; Yan, H.; Ma, Chao; Ren, Z. Y.; Gao,
X. A.; Huang, G. S.; Liang, Y. M. J. Org. Chem. 2012, 77, 2024.
(12) Via Intramolecular Dehydrogenative Aminooxygenation: (a)
Wang, H.; Wang, Y.; Liang, D.; Liu, L.; Zhang, J.; Zhu, Q. Angew.
Chem., Int. Ed. 2011, 50, 5678. From 1-(2-alkynyl)-2-(aminomethyl)-
imidazoles: (b) Galons, H.; Bergerat, I.; Combet, F. C.; Miocque, M.
Synthesis 1982, 12, 1103. From 1-acylimidazoles with dialkyl acetylene-
dicarboxylates: (c) Knoelker, H. J.; Boese, R.; Doering, D.; El-Ahl,
A. A.; Hitzemann, R.; Jones, P. G. Chem. Ber. 1992, 125, 1939.
(13) (a) Jia, J.; Ge, Y.; Tao, X. T.; Wang, J. W. Heterocycles 2010, 81,
185. (b) Koubachi, J.; El Kazzouli, S.; Berteina-Raboin, S.; Mouaddib,
A.; Guillaumet, G. Stud. Cercet. Stiint.: Chim. Ing. Chim., Biotehnol.,
Ind. Aliment. 2006, 7, 895.
We began by treating MBH acetate 1a with aminopyr-
idine 5a under different conditions (Table 1) and were
pleased to note the formation of imidazopyridine 6a as the
(15) Uncatalyzed or organocatalyzed, recent articles: (a) Singh, B.;
Chandra, A.; Singh, R. M. Tetrahedron 2011, 67, 2441. (b) Deng, H.-P.;
Wei, Y.; Shi, M. Eur. J. Org. Chem. 2011, 10, 1956. (c) Wu, C.; Zeng, H.;
Liu, L.; Wang, D.; Chen, Y. Tetrahedron 2011, 67, 1231. (d) Guo, Y.;
Shao, G.; Li, L.; Wu, W.; Li, R.; Li, J.; Song, J.; Qiu, L.; Prashad, M.;
Kwong, F. Y. Adv. Synth. Cat. 2010, 352, 1539. (e) Ge, S.-Q.; Hua,
Y.-Y.; Xia, M. Synth. Commun. 2010, 40, 1954.
(16) Metal (Pd) catalyzed: (a) Cao, H.; Vieira, T. O.; Alper, H. Org.
Lett. 2011, 13, 11. (b) Rajesh, S; Banerji, B.; Iqbal, J. J. Org. Chem. 2002,
67, 7852.
(17) For MBH reactions of nitroalkenes with carbonyl compounds,
with formaldehyde: (a) Rastogi, N.; Namboothiri, I. N. N.; Cojocaru,
M. Tetrahedron Lett. 2004, 45, 4745. (b) Mohan, R.; Rastogi, N.;
Namboothiri, I. N. N.; Mobin, S. M.; Panda, D. Bioorg. Med. Chem.
2006, 14, 8073. With other nonenolizable carbonyl compounds: (c) Deb,
I.; Dadwal, M.; Mobin, S. M.; Namboothiri, I. N. N. Org. Lett. 2006, 8,
1201. (d) Deb, I.; Shanbhag, P.; Mobin, S. M.; Namboothiri, I. N. N.
Eur. J. Org. Chem. 2009, 4091. (e) Kuan, H. -H.; Reddy, R. J.; Chen, K.
Tetrahedron 2010, 66, 9875.
(14) Selected recent reviews: (a) Basavaiah, D.; Veeraraghavaiah, G.
Chem. Soc. Rev. 2012, 41, 68. (b) Basavaiah, D.; Reddy, B. S.; Badsara,
S. S. Chem. Rev. 2010, 110, 5447. (c) Rios, R. Catal. Sci. Tech. 2012, 2,
267. (d) Limberakis, C. Name Reactions for Homologations; Li, J. J. Eds.;
John Wiley & Sons, Inc.: New York, 2009; Pt. 1, p 350. (e) Declerck, V.;
Martinez, J.; Lamaty, F. Chem. Rev. 2009, 109, 1. (f) Singh, V.; Batra, S.
Tetrahedron 2008, 64, 4511.
(18) (a) Huang, W.-Y.; Chen, Y.-C.; Chen, K. Chem. Asian J. 2012, 7,
688. (b) Nair, D. K.; Mobin, S. M.; Namboothiri, I. N. N. Tetrahedron
Lett. 2012, 53, 3349 and the references cited therein.
Org. Lett., Vol. 14, No. 17, 2012
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