ORGANIC
LETTERS
2001
Vol. 3, No. 18
2847-2850
Asymmetric Synthesis of
Trifluoromethylated Allylic Amines Using
r,â-Unsaturated
N-tert-Butanesulfinimines
G. K. Surya Prakash,* Mihirbaran Mandal, and George A. Olah*
Donald P. and Katherine B. Loker Hydrocarbon Research Institute and
Department of Chemistry, UniVersity of Southern California, UniVersity Park,
Los Angeles, California 90089-1661
Received June 15, 2001
ABSTRACT
The trifluoromethide ion generated in situ from TMSCF3 and TBAT (tetrabutylammonium triphenyldifluorosilicate), as well as TMAF
(tetramethylammonium fluoride), adds to the r,â-unsaturated N-tert-butanesulfinimines exclusively in a 1,2 fashion with high diastereoselectivities,
affording the first examples of chiral trifluoromethylated allylic amines.
Allylic amines, because of their multiple functionalities, are
the focus of numerous studies. A range of useful products,
such as R- and â-amino acids,1,2 various alkaloids,3 and
carbohydrate derivatives4 could be obtained by their double
bond functionalizations. Therefore, there have been many
methods available for their asymmetric preparation.5 Despite
the fact that introduction of fluorine brings profound changes
in bioactive molecules,6 no method for the asymmetric
preparation of trifluoromethylated allylic amines is reported.
Although addition of vinylmetallic reagents to trifluoro-
methylated imines is a viable approach,7 the scope of this
reaction would be limited to the availability of the vinyl-
metallic derivatives. Other approaches involve multiple steps
involving low yields.8 Herein, we report a straightforward
method for the preparation of trifluoromethylated allylic
amines using trifluoromethyl-trimethylsilane (TMSCF3) as
the trifluoromethide ion source.
(6) Importance of fluorine in medicinal chemistry: (a) McCarthy, J.
Utility of Fluorine In Biologically ActiVe Molecules; Division of Fluorine
Chemistry Tutorial, 219th National Meeting of the American Chemical
Society, San Francisco, March 26, 2000. (b) Filler, R.; Kobayashi, Y.;
Yagulpolskii, Y. L. Organofluorine Compounds in Medicinal Chemistry
and Biomedical Applications; Elsevier: Amsterdam, 1993. (c) Banks, R.
E.; Smart, B. E.; Tatlow, J. C. Organofluorine Chemistry: Principles and
Commercial Applications; Plenum Press: New York, 1994. (d) Hudlicky,
M.; Pavlath, A. E. Chemistry of Organic Fluorine Compounds II. A Critical
Review; ACS Monograph 187; American Chemical Society: Washington,
DC, 1995. (e) Welch, J. T., Ed. SelectiVe Fluorination in Organic and
Bioorganic Chemistry, ACS Symposium Series 456; American Chemical
Society: Washington, DC, 1991.
(7) There is no report on the addition of vinylmetallic derivatives to the
trifluoromethylated imines. For the addition of allylmetal to trifluoro-
methylated ketimines: see, Felix, C.; Laurent, A.; Lesniak, S.; Mison, P.
J. Chem. Res., Synop. 1991, 32.
(8) (a) Xu, Y.; Dolbier, W. R., Jr. J. Org. Chem. 2000, 65, 2134. (b)
Kumadaki, I.; Jonoshita, S.; Harada, A.; Omote, M.; Ando, A. J. Fluorine
Chem. 1999, 97, 61.
(1) Allylic amines to amino acids: (a) Hayashi, T.; Yamamoto, A.; Ito,
Y.; Nishioka, E.; Miura, H.; Yanagi, K. J. Am. Chem. Soc. 1989, 111, 6301.
(b) Jumnah, R.; Williams, J. M. J.; Williams, A. C. Tetrahedron Lett. 1993,
34, 6619. (c) Bower, J. F.; Jumnah, R.; Williams, J. M. J. J. Chem. Soc.,
Perkin Trans. 1 1997, 1411.
(2) Burgess, K.; Liu, L. T.; Pal, B. J. Org. Chem. 1993, 58, 4758.
(3) Alkaloids: (a) Magnus, P.; Lacour, J.; Coldham, I.; Mugrage, B.;
Bauta, W. B. Tetrahedron 1995, 51, 11087. (b) Trost, B. M. Angew. Chem.
1989, 101, 1199.
(4) Carbohydrate derivatives: Trost, B. M.; Van Vranken, D. L. J. Am.
Chem. Soc. 1993, 115, 444.
(5) For a recent review, see: Johannsen, M.; Jørgensen, K. A. Chem.
ReV. 1998, 98, 1689. For a recent example of an enantioselective approach
to allylic amines, see: Evans, P. A.; Robinson, J. E.; Nelson, J. D. J. Am.
Chem. Soc. 1999, 121, 6761.
10.1021/ol010134x CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/09/2001