A. Saito et al. / Tetrahedron Letters 44 (2003) 5449–5452
5451
Scheme 3.
ment of 15, less hindered F ring ester was first cleaved
and the following DIBAL treatment furnished 6 in 77%
yield. All the spectral data [NMR, IR, mass] collected
for 6 were identical with those of authentic samples
reported before.1b Compound 6 was finally converted
into 3,4-cis-(+)-catechin-(4b8)-(+)-catechin dimer
(7)16 by Pd(OH)2–catalyzed hydrogenolysis in 67%
yield.
8. Fonknechten, G.; Moll, M.; Cagniant, D.; Kirsch, G.;
Muller, J. F. J. Inst. Brew. 1983, 89, 424–431.
9. Kawamoto, H.; Nakatsubo, F.; Murakami, K. Mokuzai
Gakkaishi 1991, 37, 488–493.
10. Kozikowski reported stereocontrolled synthesis of epi-
catechin-4a,8-epicatechin. Kozikowski, A. P.; Tuckman-
tel, W.; Hu, Y. J. Org. Chem. 2001, 66, 1287–1296.
11. A typical procedure for Intramolecular TMSOTf-cata-
lyzed coupling: To a solution of (2R,3S)-5,7,3%,4%-tetra-
benzyloxy-flavan-3-yl (2R,3S,4S)-5,7,3%,4%-tetrabenzyloxy-
4-ethoxyethyloxy-flavan-3-yl glutarate (206 mg, 0.139
mmol) in CH2Cl2 (80 mL) was added dropwise
TMSOTf (0.28 mL, 0.14 mmol, 0.5 M solution in
CH2Cl2) at −20°C. After stirring for 10 min, the pale
yellow reaction mixture was quenched with sat.
NaHCO3. The aq. solution was extracted with CHCl3
and the organic phase was washed with water and
brine, and dried (Na2SO4). Filtration, concentration
and silica gel column purification (hexane/EtOAc, 6/1
to 2/1) afforded a 190 mg (0.136 mmol, 98%) of a
mixture of 15 as a amorphous solid.
Conclusion
The TMSOTf-catalyzed intramolecular one-to-one cou-
pling method was developed. (+)-Catechin and (+)-cate-
chin condensation produced 3,4-cis condensed product.
This method will be expected to develop a good
oligomerization method.
References
12. Data for 15: [h]D24=+87.6 (c 1.14, CHCl3); 1H NMR
(400 MHz, CDCl3) 7.52–6.90 (43H, m), 6.86–6.84 (1H,
m), 6.26 (1H, s, D6), 6.21 (1H, d, J=8.5 Hz), 6.02
(1H, d, J=2.2 Hz, A6), 5.88 (1H, d, J=2.2 Hz, A8),
5.50 (1H, dd, J=7.1, 10.4 Hz, C3), 5.40 (1H, d, J=7.1
Hz, C4), 5.39 (1H, d, J=1.7 Hz, F2), 5.32 (1H, dd,
J=1.7, 4.2 Hz, F3), 5.31 (1H, d, J=10.4 Hz, C2), 5.12
(2H, s), 5.09 (2H, s), 5.01 (1H, d, J=12.0 Hz), 4.98
(1H, d, J=11.7 Hz), 4.97 (1H, d, J=11.7 Hz), 4.94
(1H, d, J=12.0 Hz), 4.82–4.73 (4H, m), 4.66 (1H, d,
J=12.0 Hz), 4.31 (1H, d, J=12.0 Hz), 2.84 (1H, d,
J=17.8 Hz, F4), 2.36 (1H, dd, J=4.2, 17.8 Hz, F4),
2.39–2.20 (3H, m), 2.07–1.96 (1H, m), 1.93–1.75 (2H,
m); 13C NMR (100 MHz, CDCl3) 172.8, 171.0, 158.3,
157.4, 156.6, 155.9, 155.8, 152.6, 148.9, 148.8, 148.4,
1. (a) Saito, A.; Nakajima, N.; Tanaka, A.; Ubukata, M.
Biosci. Biotechnol. Biochem. 2002, 66, 1764–1767; (b)
Saito, A.; Nakajima, N.; Tanaka, A.; Ubukata, M.
Tetrahedron 2002, 58, 7829–7837.
2. Harborne, J. B. The Flavonoids: Advances in Research
from 1986; Chapman and Hall: London, 1993.
3. Harborne FRS, J. B.; Baxter, H. The Handbook of
Natural Flavonoids; John Wiley & Sons: NY, 1999.
4. Ariga, T.; Koshiyama, I.; Fukushima, D. Agric. Biol.
Chem. 1988, 52, 2717–2722.
5. Zhao, J.; Wang, J.; Chen, Y.; Agarwal, R. Carcinogen-
esis 1999, 20, 1737–1745.
6. Thompson, R. S.; Jacques, D.; Halsam, E.; Tanner, R.
J. N. J. Chem. Soc., Perkin Trans. 1 1972, 1387–1399.
7. Eastmond, R. J. Inst. Brew. 1974, 80, 188–192.