COMMUNICATIONS
D. L. VanVranken, Chem. Rev. 1996, 96, 395;
C. G. Frost, J. Howarth, J. M. J. Williams,
Tetrahedron: Asymmetry 1992, 3, 1089.
[2] B. M. Trost, Acc. Chem. Res. 1996, 29, 355.
[3] B. M. Trost, M. Lautens, J. Am. Chem. Soc.
1987, 109, 1469; B. M. Trost, M. Lautens, J.
Am. Chem. Soc. 1982, 104, 5543.
[4] J. Lehmann, G. C. Lloyd-Jones, Tetrahedron
1995, 51, 8863.
[5] For enantioselective substitution reactions
with Mo: B. M. Trost, I. Hachiya, J. Am.
Chem. Soc. 1998, 120, 1104; B. M. Trost, S.
Hildbrand, K. Dogra, J. Am. Chem. Soc. 1999,
121, 10416; for asymmetric W: G. C. Lloyd-
Jones, A. Pfaltz, Angew. Chem. 1995, 107, 534;
Angew. Chem. Int. Ed. Engl. 1995, 34, 462.
[6] R. Takeuchi, N. Ve, K. Tanabe, K. Yamashita,
N. Shiga, J. Am. Chem. Soc. 2001, 123, 9525;
R. Takeuchi, M. Kashio, J. Am. Chem. Soc.
1998, 120, 8647; B. Bartels, G. Helmchen,
Chem. Commun. 1999, 741. J. P. Janssen, G.
Helmchen, Tetrahedron Lett. 1997, 38, 8025.
[7] P. A. Evans, J. D. Nelson, Tetrahedron Lett.
1998, 39, 1725; P. A. Evans, D. K. Leahy, J.
Am. Chem. Soc. 2000, 122, 5012; P. A. Evans,
L. Kennedy, J. Org. Lett. 2000, 2, 2213; P. A.
Evans, L. J. Kennedy, J. Am. Chem. Soc. 2001,
123, 1234.
Scheme 1. Synthesis of antidepressants. a) CH3I, K2CO3, CH3OH, RT; b) LDA, THF, HMPA, À50
to 08C; c) n-C4H9Li, ClCO2CH3, THF, À78 to 08C; d) 1 mol% 7, p-CF3C6H4OTMS, 1 mol% TBAT,
neat, 358C; e) 1 mol% 7, o-CH3C6H4OTMS, 5 mol% (n-C4H9)4NCl, 10 mol% (C2H5)3N, neat, 358C;
f) 9-BBN-H, THF, 358C then KOH, H2O2, 08C; g) CH3SO2Cl, (C2H5)3N, CH2Cl2, 08C then CH3NH2,
CH3OH, 708C. LDA lithium diisopropylamide, HMPA hexamethylphosphoramide, 9-BBN-
H 9-borabicyclo[3.3.1]nonane.
[8] D. W. Robertson, N. D. Jones, J. K. Swartzen-
druber, K. S. Yang, D. T. Wong, J. Med. Chem.
1988, 31, 185. For the biological activity of the
single-enantiomer drug: D. W. Robertson, J. H. Krushinski, R. W.
Fuller, J. D. Leander, J. Med. Chem. 1988, 31, 1412.
desilylating agent (tetrabutylammonium triphenyldifluorosil-
icate (TBAT) or tetrabutylammonium chloride (TBAC)) with
1 mol% of 7 under neat conditions effected the desired
reaction. The reaction of the trimethylsilyl ether of p-
trifluorocresol gave a 7:1 b/l ratio from which 15a was
isolated in 81% yield.
Standard hydroboration, oxidation, and substitution pro-
vided (À)-fluoxetine (17). Switching to the o-cresol system
similarly gave a 6:1 b/l ratio from which 15b was isolated in
81% yield. In both cases, excellent chirality transfer is
observed, demonstrating the effectiveness of our catalyst for
both carbon and heteroatom nucleophiles.
The ruthenium-catalyzed allylic alkylation differs from
previous catalytic systems in several important respects. Like
Pd, Mo, and W- but unlike Rh–regioselectivity is not highly
dependent on the nature of the starting carbonate. Unlike Pd
and Mo, but like Rh and W, substitution of the scalemic chiral
substrate occurs with high net retention of configuration.
Heteroatom nucleophiles which fail with Mo and W succeed
with this system. Thus, this catalyst nicely complements the
previously developed systems. Importantly, reactions proceed
extremely well under mild conditions with 1 mol% of catalyst.
The solvent-free conditions are commensurate with the ideals
of green chemistry. The practicality of the methodology is
illustrated by a novel synthesis of (R)-fluoxetine and (R)-
tomoxetine starting from inexpensive ephedrine using a
heretofore unknown elimination to generate the allyl alcohol
of high enantiopurity.
[9] S. W. Zhang, T. Mitsudo, T. Kondo, Y. Watanabe, J. Organomet. Chem.
1995, 485, 55; S. W. Zhang, T. Mitsudo, T. Kondo, Y. J. Watanabe,
Organomet. Chem. 1993, 450, 197. A report has appeared very recently
using a planar chiral ruthenium complex for the enantioselective
alkylation of a symmetric meso-type allyl unit: Y. Matsushima, K.
Onitsuka, T. Kondo, T. Mitsudo, S. J. Takahashi, J. Am. Chem. Soc.
2001, 123, 10405.
[10] T. Kondo, Y. Morisaki, S. Uenoyama, K. Wada, T. Mitsudo, J. Am.
Chem. Soc. 1999, 121, 8657.
[11] S. K. Kang, D. Y. Kim, R. K. Hong, P. S. Ho, Synth. Commun. 1996, 26,
3225.
[12] For synthetic efforts towards both drugs, see the following and
references therein: H. L. Liu, B. H. Ho, T. Anthonsen, J. Chem. Soc.
Perkin Trans. 1 2000, 11, 1767.
[13] A. Hoffman, Chem. Ber. 1881, 14, 166; K. Hayakawa, I Fuji, J.
Kanematsu, J. Org. Chem. 1983, 48, 166.
[14] F. Bracher, T. Litz, Bioorg. Med. Chem. 1996, 4, 877.
[15] R. Chenevert, G. Fortier, R. B. Rhlid, Tetrahedron 1992, 48, 6769.
Received: January 8, 2002 [Z18496]
[1] For general reviews of Pd-catalyzed allylic substitution: S. A. God-
leski in Comprehensive Organic Synthesis, Vol. 4 (Eds.: B. M. Trost, I.
Fleming, M. F. Semmelhack), Pergamon, Oxford, 1991; B. M. Trost,
Angew. Chem. Int. Ed. 2002, 41, No. 6
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
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