reaction of 1g or 1h as the reaction substrate, this reaction in
entry 12 gave the product with a lower yield, perhaps due to a
strong steric hindrance from the two phenyl groups.
Notes and references
z Representative procedure for FeCl3-catalyzed construction func-
tionalized 4H-chromene: FeCl3 (8.1 mg, 0.05 mmol), and 0.50 g of 4 A
MS were added to a solution of 1a (0.5 mmol) and 2a (1.0 mmol) in
freshly distilled CH2Cl2 (1.5 mL). The resulting mixture was refluxed
for 12 h, then cooled to room temperature and quenched with
saturated NaHCO3, and the mixture was extracted with CH2Cl2 twice.
The combined organic extracts were dried over Na2SO4 and filtered.
Solvents were evaporated under reduced pressure. The residue was
purified by column chromatography on silica gel using PE–EtOAc
(10 : 1, v/v) as eluent to give 3a as a colorless oil (129.0 mg, 88%).
1H NMR (CDCl3, 300 MHz, ppm): d 7.13–7.11 (m, 4 H), 7.04–6.99
(m, 2 H), 6.94–6.85 (m, 3 H), 4.93 (s, 1 H), 4.00–3.95 (m, 2 H), 2.39 (s,
3 H), 1.06 (t, J = 7.2 Hz, 3 H); 13C NMR (CDCl3, 75 MHz, ppm): d
167.2, 160.1, 149.6, 146.8, 129.4, 128.5, 128.0, 127.6, 126.6, 125.0,
124.6, 116.3, 106.3, 60.2, 41.7, 19.6, 14.2; IR (liquid film, cmꢂ1): v =
3063, 2979, 2872, 1711, 1643, 1585, 1488, 1456, 1380, 1331, 1288, 1218,
1106, 1064, 985, 754, 698, 621; HRMS calc. C19H18O3 (M+): 294.1256.
Found: 294.1263.
Subsequently, we set out to study the scope and limitation
of b-ketoester or b-diketone reactants in detail. As shown in
Table 3, a range of different b-ketoesters or b-diketones were
employed as the reaction substrates and the corresponding
reactions were carried out smoothly with excellent yields. For
b-ketoesters, no significant influences of various b-ketoesters
were observed except for methyl 4-methyl-3-oxopentanoate
(Table 3, entry 5) probably due to the bigger hindrance
adjacent to the carbonyl group. For b-diketones, higher yields
were obtained compared to b-ketoesters, which showed that
the reaction activity of b-diketones is higher that of b-keto-
esters in this annulation reaction.
In conclusion, we have developed a novel annulation for
convenient and effective construction of functionalized 4H-
chromenes from easily available substrates under mild condi-
tions. The use of a simple iron salt as catalyst renders the
protocol suitable for large-scale synthesis, providing a valu-
able access to assemble biologically active molecules.
This work was supported by the National Natural Science
Foundation of China (20628202).
1 (a) E. E. Schweizer and O. Meeder-Nycz, in Chromenes, Chro-
manes, Chromones, ed. G. P. Ellis, Wiley-Interscience, New York,
1977; (b) A. F. Benslimane, Y. F. Pouchus, J.-F. Verbist, J.-Y.
Petit, J. D. Brion and L. Welin, J. Clin. Pharmacol., 1995, 35,
298–301; (c) K. C. Nicolaou, J. A. Pfefferkorn, A. J. Roecker, G.
Q. Cao, S. Barluenga and H. J. Mitchell, J. Am. Chem. Soc., 2000,
122, 9939–9953; (d) V. Rukachaisirikul, M. Kamkaew, D.
Sukavisit, S. Phongpaichit, P. Sawangchote and W. C. Taylor, J.
Nat. Prod., 2003, 66, 1531–1535.
Table
3
Reaction of 2-(hydroxy(phenyl)methyl)phenol 1a with
2 (a) I. R. Hardcastle, X. l. Cockcroft, N. J. Curtin, M. D. El-Murr, J.
J. Leahy, M. Stockley, B. T. Golding, L. Rigoreau, C. Richardson, G.
C. M. Smith and R. J. Griffin, J. Med. Chem., 2005, 48, 7829–7846;
(b) D. J. Maloney, S. X. Chen and S. M. Hecht, Org. Lett., 2006, 8,
1925–1927; (c) M. Kidwai, S. Saxena, M. K. R. Khan and S. S.
Thukral, Bioorg. Med. Chem. Lett., 2005, 15, 4295–4298.
3 (a) B. Appel, N. N. R. Saleh and P. Langer, Chem.–Eur. J., 2006,
12, 1221–1236; (b) C. F. Nising, U. K. Ohnemuller and S. Brase,
Angew. Chem., Int. Ed., 2006, 45, 307–309.
different b-ketoesters or b-diketones 2a
4 (a) E. J. Corey and L. I. Wu, J. Am. Chem. Soc., 1993, 115,
9327–9328; (b) Dachriyanus, Salni, M. V. Sargent, B. W. Skelton,
I. Soediro, M. Sutisna, A. H. White and E. Yulinah, Aust.
J. Chem., 2002, 55, 229–232; (c) F. Shaheen, M. Ahmad, S. N.
Khan, S. S. Hussain, S. Anjum, B. Tashkhodjaev, K. Turgunov,
M. N. Sultankhodzhaev, M. I. Choudhary and A. Rahman, Eur. J.
Org. Chem., 2006, 2371–2377; (d) J.-L. Wang, D. X. Liu, Z.-J.
Zhang, S. M. Shan, X. B. Han, S. M. Srinivasula, C. M. Croce, E.
S. Alnemri and Z. W. Huang, Proc. Natl. Acad. Sci. USA, 2000, 97,
7124–7129.
5 Y. Nishibayashi, Y. Inada, M. Hidai and S. Uemura, J. Am. Chem.
Soc., 2002, 124, 7900–7901.
6 (a) Y.-L. Shi and M. Shi, Org. Lett., 2005, 7, 3057–3060; (b) Y.-W.
Guo, Y.-L. Shi, H.-B. Lia and M. Shi, Tetrahedron, 2006, 62,
5875–5882; (c) Y.-L. Shi and M. Shi, Org. Biomol. Chem., 2007, 5,
1499–1504; (d) G.-L. Zhao, Y.-L. Shi and M. Shi, Org. Lett., 2005,
7, 4527–4530; (e) Y.-L. Shi and M. Shi, Chem.–Eur. J., 2006, 12,
3374–3378.
7 W. A. L. V. Otterlo, E. L. Ngidi, S. Kuzvidza, G. L. Morgans, S. S.
Moleele and C. B. Koning, Tetrahedron, 2005, 61, 9996–10006.
8 Y. W. Fang and C. Z. Li, J. Org. Chem., 2006, 71, 6427–6431.
9 L.-W. Ye, X.-L. Sun, C.-Y. Zhu and Y. Tang, Org. Lett., 2006, 8,
3853–3856.
10 (a) I. Iovel, K. Mertins, J. Kischel, A. Zapf and M. Beller, Angew.
Chem., Int. Ed., 2005, 44, 3913–3917; (b) K. Mertins, I. Iovel, J.
Kischel, A. Zapf and M. Beller, Adv. Synth. Catal., 2006, 348,
691–695; (c) K. Motokura, N. Nakagiri, T. Mizugaki, K. Ebitani
and K. Kaneda, J. Org. Chem., 2007, 72, 6006–6015.
11 (a) M. Yasuda, T. Somyo and A. Baba, Angew. Chem., Int. Ed.,
2006, 45, 793–796; (b) K. Motokura, N. Fujita, K. Mori, T.
Mizugaki, K. Ebitani and K. Kaneda, Angew. Chem., Int. Ed.,
2006, 45, 2605–2609; (c) J. Kischel, K. Mertins, D. Michalik, A.
Zapf and M. Beller, Adv. Synth. Catal., 2007, 349, 865–870; (d) M.
Rueping, B. J. Nachtsheim and A. Kuenkel, Org. Lett., 2007, 9,
825–828.
a
Reaction conditions: 2-(hydroxy(phenyl)methyl)phenol 1 (0.5 mmol),
b-ketoester or b-diketone 2 (1.0 mmol), FeCl3 (0.05 mmol), CH2Cl2
(1.5 ml), 4 A MS (0.5 g), reflux, 12 h. bYield of isolated product.
ꢁc
This journal is The Royal Society of Chemistry 2008
Chem. Commun., 2008, 5381–5383 | 5383