M. Mogi et al. / Tetrahedron: Asymmetry 15 (2004) 3715–3717
3717
Tepper, P. G.; Dijkstra, D.; Damsma, G.; Wikstrom, H.;
Pugsley, T. A.; Akunne, H. C.; Heffner, T. G.; Glase, S. A.;
Wise, L. D. J. Med. Chem. 1996, 39, 4233–4237.
served among the substrates 3, 4, 6, and 8, a notable in-
crease in selectivity was seen for 6-methoxy-2-tetralone 5
with 92% ee (Table 2, entry 9) and 8-methoxy-2-tetra-
lone 7 affording (2R)-8-methoxy-2-tetralol with 98% ee
(Table 2, entry 11). This new finding of the enantioselec-
tivity toward 8-methoxy-2-tetralone 7 is especially valu-
able for the study of serotonin (5-HT) and dopamine
(DA) receptor agonists since substrate 7 is readily avail-
able either commercially or by the reported procedure of
Nichols and co-workers9 while the obtained enantiomer-
ically pure 8-methoxy-2-tetralol can be easily converted
to the chiral 8-methoxy-2-aminotetralin derivatives by
the known method in good yields.5
2. Liu, Y.; Yu, H.; Mohell, N.; Nordvall, G.; Lewander, T.;
Hacksell, U. J. Med. Chem. 1995, 38, 150–160.
3. (a) Terashima, S.; Tanno, N.; Koga, K. Chem. Lett. 1980,
981–984; (b) Kawasaki, M.; Suzuki, Y.; Terashima, S.
Chem. Lett. 1984, 239–242; (c) Fujii, A.; Hashiguchi, S.;
Uematsu, N.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc.
1996, 118, 2521–2522; (d) Palmer, M.; Walsgrove, T.; Wills,
M. J. Org. Chem. 1997, 62, 5226–5228.
4. Manitto, P.; Speranza, G.; Monti, D.; Fontana, G.;
Panosetti, E. Tetrahedron 1995, 51, 11531–11546.
5. Orsini, F.; Sello, G.; Travaini, E.; Gennaro, P. D. Tetra-
hedron: Asymmetry 2002, 13, 253–259.
6. For its excellent review, see: (a) Noyori, R.; Yamakawa,
M.; Hashiguchi, S. J. Org. Chem. 2001, 66, 7931–7944; (b)
Palmer, M. J.; Wills, M. Tetrahedron: Asymmetry 1999, 10,
2045–2061.
3. Conclusion
7. Hashiguchi, S.; Fujii, A.; Takehara, J.; Ikariya, T.; Noyori,
R. J. Am. Chem. Soc. 1995, 117, 7562–7563.
In conclusion, an application of the asymmetric transfer
hydrogenation for the preparation of various methoxy
substituted chiral 2-tetralols, was evaluated. The result-
ing materials are interesting intermediates for the chiral
synthesis of many serotonin and dopamine agonists.
The reaction conditions using the [RuCl2(benzene)]2
complex with (R,R)-N-(2-amino-1,2-diphenylethyl)-p-
toluenesulfonamide (Noyori ligand) were found to give
the best results, with moderate to excellent enantiomeric
excesses, most notably for (2R)-8-methoxy-2-tetralol,
which was obtained in 98% ee.
8. A general procedure for the asymmetric transfer hydrogen-
ation of 2-tetralones: A mixture of benzene or p-cymene
ruthenium(II) chloride dimer (0.0057mmol) and (R,R)-N-
(2-amino-1,2-diphenylethyl)-p-toluenesulfonamide or (1S,
2R)-(À)-cis-1-amino-2-indanol (0.011mmol) in 2-propanol
(2.0mL) was stirred at 80°C for 30min under Ar. In a
separate flask,
a
solution of potassium hydroxide
(0.057mmol) in 2-propanol (1.5mL) was stirred at 50°C
for 30min. To a solution of the prochiral tetralone
(0.284mmol) in 2-propanol (5.0mL) was added the catalyst
mixture followed by KOH solution and stirred at 50°C for
45min. After the reaction, the mixture was immediately
passed through a pad of Celite and silica gel and then
concentrated under reduced pressure. The obtained product
was purified by silica gel preparatory TLC to afford the
chiral tetralol.
References
1. (a) Arvidsson, L. E.; Hacksell, U.; Nilsson, J. L. G.; Hjorth,
S.; Carlsson, A.; Lindberg, P.; Sanchez, D.; Wilkstroem, H.
J. Med. Chem. 1981, 24, 921–923; (b) van Vliet, L. A.;
9. Lee, S.; Frescas, S. P.; Nichols, D. E. Synth. Commun. 1995,
25, 2775–2780.