Y.-S. Hon, R. Devulapally / Tetrahedron Letters 50 (2009) 5713–5715
5715
R1
R5
R1
R5
was determined by 2D-NOESY and from the coupling constant of
C(4)–H and C(3)–H. In summary, 4-aryl-2-hydroxybutanal diethyl
acetal 6 was easily prepared from the reaction of benzyl organome-
tallic reagent and glycidaldehyde diethyl acetal 4. The diluted solu-
tion of acetal 6 was treated with TiCl4 to give 2-tetralones in good
yields. A variety of substituents can be introduced at all positions
of 2-tetralone except C(1) by this method. The 2-tetralone forma-
tion involves tandem oxonium ion formation, intramolecular Fri-
edel–Crafts alkylation, deethoxylation, and tautomerization in
the same flask (Fig. 2).3 To the best of our knowledge, this two-step
synthetic sequence is the most efficient and direct way to prepare
2-tetralone derivatives.
R2
R3
R
R2
R3
oxonium ion
R
formation
TiCl4
OH
O
HCl
OEt
OEt
R4
6
O
R4
TiCl3
O
Et
R5
Et
R1
R1
R5
R2
R3
R
intramolecular
Friedel-Crafts
alkylation
R2
R3
R
O
O
R4
[Ti]
O
R4
Ti(OEt)Cl3
R5
Et
O
Et
R1
R5
R1
R2
R3
R
R2
R
deethoxy-
lation
TiCl4
Acknowledgments
R3
O
O
H
EtOTiCl3
We are grateful to the National Science Council, National Chung
Cheng University, and Academia Sinica for the financial support.
R4
R1
R4
[Ti]
[Ti]
O
TiCl4
Et
R5
R1
R5
R2
R
O
R2
R3
R
workup
References and notes
tautomerization
R3
O
H
1. Silveira, C. C.; Braga, A. L.; Kaufman, T. S.; Lenardao, E. J. Tetrahedron 2004, 60,
8295–8328. and references cited therein.
R4
R4
[Ti]
7
2. (a) Hon, Y. S.; Wang, Y. C. Tetrahedron Lett. 2005, 46, 1365–1368; (b) Hon, Y. S.;
Wang, Y. C.; Wu, K. J. J. Chin. Chem. Soc. 2008, 55, 896–914; (c) Hon, Y. S.; Kao, C.
Y. Tetrahedron Lett. 2009, 50, 748–751.
Figure 2. A plausible mechanism for 2-tetralone 7 formation from compounds 6.
3. Hon, Y. S.; Devulapally, R. Tetrahedron Lett. 2009, 50, 2831–2834.
4. (a) van Allan, J. A. Org. Synth. Collect. 1963, 4, 21–22; (b) Karimi, B.; Seradj, H.;
Ebrahimian, G.-R. Synlett 1999, 1456–1458.
5. (a) Durrwachter, J. R.; Drueckhammer, D. G.; Nozaki, K.; Sweers, H. M.; Wong, C.-H.
J. Am. Chem. Soc. 1986, 108, 7812–7818; (b) Silverman, R. B.; Ding, C. Z. J. Am. Chem.
Soc. 1993, 115, 4571–4576.
6. (a) Posner, G. H. Org. React. 1975, 22, 253–400; (b) Liu, Z.; Sayre, L. M. Chem. Res.
Toxicol. 2003, 16, 232–241.
7. Suh, Y. S.; Lee, J.-s.; Kim, S. H.; Rieke, R. D. J. Organomet. Chem. 2003, 684, 20–36.
and reference cited therein.
4b followed by TiCl4-promoted cyclization to give 6-methoxy-3-
methyl-2-tetralone (7q) in 79% yield (Table 2, entry 2).
In order to introduce the substituents at both the C(3)- and
C(4)-positions of 2-tetralone, the
and 1,2-disubstituted oxirane 4b were used as starting materials.
-Phenylbenzyl chloride (5o) was treated with Rieke Mg by the
standard protocol, and the resulting Grignard reagent was reacted
-hydroxy acetal 6o00 in 56%
a-substituted-benzyl chloride
a
8. (a) Rieke, R. D.; Li, P. T.-Z.; Burns, T. P.; Uhm, S. T. J. Org. Chem. 1981, 46, 4323–
4324. and references cited therein; (b) Rieke, R. D. Acc. Chem. Res. 1977, 10, 301–
306; (c) Rieke, R. D.; Hanson, M. V. Tetrahedron 1997, 53, 1925–1956; (d) Rieke,
R. D. Science 1989, 246, 1260–1264 .
with oxirane 4b at ꢀ50 °C to give
a
yield. Further treatment with TiCl4 gave 3,4-dimethyl-2-tetralone
(7o00) as a mixture of two diastereomers (syn/anti 1/2.8) in 58%
yield (Table 2, entry 3). The stereochemistry of the major isomer