A. R. Jagdale, A. Sudalai / Tetrahedron Letters 48 (2007) 4895–4898
4897
OH
Ph
O
R'
O
R'
p
-TSA, 125 °C
or
Ph
OH
Ph
O
3 h, No solvent
O
O
R'
2
4
3
1
Yield (%)
R'
3
99
-
4
-
98
H
NO2
Scheme 1. p-Toluenesulfonic acid mediated reaction of cinnamic acid with phenols.
3. (a) Yoshida, T.; Ohbayashi, G.; Ishihara, K.; Ohwashi,
W.; Haba, K.; Okano, Y.; Shingu, T.; Okuda, T. Chem.
Pharm. Bull. 1991, 39, 2233; (b) Okuda, T.; Hatano, T.;
Yakazi, K. Chem. Pharm. Bull. 1983, 31, 333; (c) Saijio,
R.; Nonaka, G.-I.; Nishioka, I. Chem. Pharm. Bull. 1989,
37, 2063; (d) Iinuma, M.; Tanaka, T.; Asai, F. Phyto-
chemistry 1994, 36, 941; (e) Iinuma, M.; Tanaka, T.;
Mizuno, M.; Katsuzaki, T.; Ogawa, H. Chem. Pharm.
Bull. 1989, 37, 1813; (f) Hsu, F.-L.; Nonaka, G.-I.;
Nishioka, I. Chem. Pharm. Bull. 1985, 33, 3142; (g)
Nonaka, G.-I.; Kawahara, O.; Nishioka, I. Chem. Pharm.
Bull. 1982, 30, 4277.
4. Vosmann, K.; Wittkamp, P.; Weber, N. J. Agric. Food
Chem. 2006, 54, 2969, and references cited therein.
5. For reviews see: (a) Jia, C.; Kitamura, T.; Fujiwara, Y.
Acc. Chem. Res. 2001, 34, 633; (b) Ritleng, V.; Sirlin, C.;
Pfeffer, M. Chem. Rev. 2002, 102, 1731.
6. (a) Li, K.; Foresee, L. N.; Tunge, J. A. J. Org. Chem. 2005,
70, 2881; (b) Oyamada, J.; Kitamura, T. Tetrahedron 2006,
62, 6918; (c) Fillion, E.; Dumas, A. M.; Kuropatwa, B. A.;
Malhotra, N. R.; Sitler, T. C. J. Org. Chem. 2006, 71, 409;
(d) Aoki, S.; Amamoto, C.; Oyamada, J.; Kitamura, T.
Tetrahedron 2005, 61, 9291; (e) Song, C. E.; Jung, D.;
Choung, S. Y.; Roh, E. J.; Lee, S. Angew. Chem., Int. Ed.
2004, 43, 6183; (f) Jia, C.; Lu, W.; Oyamada, J.; Kitamura,
T.; Matsuda, K.; Irie, M.; Fujiwara, Y. J. Am. Chem. Soc.
2000, 122, 7252; (g) Shi, Z.; He, C. J. Org. Chem. 2004, 69,
3669; (h) Jia, C.; Piao, D.; Oyamada, J.; Lu, W.;
Kitamura, T.; Fujiwara, Y. Science 2000, 287, 1992.
7. (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis;
John Wiley and Sons: New York, 1994; (b) McGuire, M.
A.; Shilcrat, S. C.; Sorenson, E. Tetrahedron Lett. 1999,
40, 3293.
blocked, alkylation occurred at the ortho position (Table
2, entry g). Other less activated substrates such as tolu-
ene failed to undergo hydroarylation. Acetanilide under-
went complete hydrolysis producing aniline. Treatment
of chalcone with anisole in the presence of p-TSA
yielded a mixture of products that was difficult to
separate.
Mechanistically, in the case of phenols, formation of
phenolic esters followed by intramolecular Friedel–
Crafts type cyclization leads to dihydrocoumarin deriv-
atives 3.5a This observation was supported by the fact
that when (E)-phenyl cinnamate was subjected to hydro-
arylation under the same reaction conditions, dihydro-
coumarin 3 was obtained. In the case of anisoles,
protonation of cinnamic acids leads to a highly electro-
philic benzylic carbon such that Friedel–Crafts type
alkylation with electron-rich anisole took place produc-
ing 3-(4-methoxyphenyl)-3-phenylpropanoic acids 7a–j.
In conclusion, we have developed a convenient, practical
and metal and solvent-free process for hydroarylation of
cinnamic acids with phenols and anisoles mediated by
p-toluenesulfonic acid affording dihydrocoumarins 3,
esters 5 and 3-(4-methoxyphenyl)-3-phenylpropanoic
acids 7a–j, respectively, in good to high yields. High reg-
ioselectivity, easy handling, broad substrate scope and
the use of cheap p-toluenesulfonic acid as acid mediator
are some of the advantages of this methodology.
8. (a) Johnston, K. M. Tetrahedron 1968, 25, 5595; (b)
Fillion, E.; Dumas, A. M.; Kuropatwa, B. A.; Malhotra,
N. R.; Sitler, T. C. J. Org. Chem. 2006, 71, 409.
9. Barluenga, J.; Andina, F.; Aznar, F. Org. Lett. 2006, 8,
2703.
Acknowledgements
A.R.J. thanks the CSIR, New Delhi for the award of
research fellowship. The authors are thankful to Dr.
B. D. Kulkarni, Head, CEPD, for his support and
encouragement.
10. Typical experimental procedure: To a 25 mL round-
bottomed flask equipped with a reflux condenser, were
charged phenol or anisole (5.5 mmol), cinnamic acid
(5 mmol), and p-toluenesulfonic acid (5 mmol). The reac-
tion mixture was heated to 125 ꢁC for 3 h. After comple-
tion (monitored by TLC), the reaction mixture was cooled
and quenched with water (50 mL) and extracted with ethyl
acetate (2 · 50 mL). The organic phase was washed with
water and brine, dried over anhydrous Na2SO4, and
concentrated under reduced pressure to afford the crude
product, which was purified by column chromatography
over silica gel (230–400 mesh) using ethyl acetate and
petroleum ether as eluent.
References and notes
1. (a) Staunton, J. In Comprehensive Organic Chemistry;
Sammes, P. G., Ed.; Pergamon: Oxford, 1979; Vol. 4, p
651; (b) Matern, U.; Luer, P.; Kreusch, D. In Compre-
¨
hensive Natural Products Chemistry; Sankawa, U., Ed.;
Pergamon: Oxford, 1999; Vol. 1, p 623.
2. Zhang, X.; Wang, H.; Song, Y.; Nie, L.; Wang, L.; Liu, B.;
Shen, P.; Liua, Y. Bioorg. Med. Chem. Lett. 2006, 16, 949.
11. Spectal data for representative compounds. Ethyl 3-(3-
chloro-2-hydroxyphenyl)-3-phenylpropanoate (5l): Yield
87%, 1H NMR (200 MHz) d 1.12 (t, J = 7.1 Hz, 3H),