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with 2f bearing a trifluoroacetyl group as N-protective
group (S up to 9.4). The advantage of trifluoroacet-
amides is in the ease of formation and in the ease of
cleavage of the amide bond. Deprotection of (+)-2f
was thus carried out in a 2.0 M solution of ammonia
in methanol affording (+)-cis-1-amino-2-indanol with-
out loss of enantiomeric excess.19
3. Fu, G. C. Acc. Chem. Res. 2004, 37, 542–547, and
references cited therein.
In order to establish whether the trifluoroacetyl group
could represent a general protecting group for the
kinetic resolution of aminoalcohols, this study has been
extended to structurally different alcohols 3–5 (Table 2).
As in previous work, KR studies gave comparable
results with solution or solid-supported catalyst for all
N-protected aminoalcohols. Selectivities obtained with
catalyst 1a were generally slightly better but sup-
ported-catalyst 1b does have the advantage of being easy
to recycle and reuse. The trifluoroacetyl group consis-
tently gives better results (Table 2, entries 1–6) than
the Cbz and Boc derivatives (entries 7–11) for a range
of protected aminoalcohols, matching results obtained
with the cis-1-amino-2-indanol series. These results form
a platform for further studies but indicate that kinetic
resolution is possible with a more easily removed pro-
tecting group.
4. Spivey, A. C.; Leese, D. P.; Zhu, F.; Davey, S. G.; Jarvest,
R. L. Tetrahedron 2004, 60, 4513–4525, and references
cited therein.
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H.; Nagaoka, Y.; Fuji, K. Chem. Commun. 2001, 2700–
2701; (b) Kawabata, T.; Stragies, R.; Fukaya, T.; Naga-
oka, Y.; Schedel, H.; Fuji, K. Tetrahedron Lett. 2003, 44,
1545–1548, and references cited therein.
6. MacKay, J. A.; Vedejs, E. J. Org. Chem. 2004, 69, 6934–
6937, and references cited therein.
7. Miller, S. J. Acc. Chem. Res. 2004, 37, 601–610, and
references cited therein.
8. Terakado, D.; Koutaka, H.; Oriyama, T. Tetrahedron:
Asymmetry 2005, 16, 1157–1165, and references cited
therein.
9. Naraku, G.; Shimomoto, N.; Hanamoto, T.; Inanaga, J.
Enantiomer 2000, 5, 135–138.
10. Jeong, K.-S.; Kim, S.-H.; Park, H.-J.; Chang, K.-J.; Kim,
K. S. Chem. Lett. 2002, 1114–1115.
11. Ishihara, K.; Kosugi, Y.; Akakura, M. J. Am. Chem. Soc.
2004, 126, 12212–12213.
12. Suzuki, Y.; Yamauchi, K.; Muramatsu, K.; Sato, M.
Chem. Commun. 2004, 2770–2771.
13. Dalaigh, C. O.; Hynes, S. J.; Maher, D. J.; Connon, S. J.
Org. Biomol. Chem. 2005, 3, 981–984.
14. Yamada, S.; Misono, T.; Iwai, T. Tetrahedron Lett. 2005,
46, 2239–2242.
15. Kano, T.; Sasaki, K.; Maruoka, K. Org. Lett. 2005, 7,
1347–1349.
16. Birman, V. B.; Jiang, H. Org. Lett. 2005, 7, 3445–3447,
and references cited therein.
17. (a) Priem, G.; Anson, M. S.; Macdonald, S. J. F.; Pelotier,
B.; Campbell, I. B. Tetrahedron Lett. 2002, 43, 6001–6003;
(b) Priem, G.; Pelotier, B.; Macdonald, S. J. F.; Anson,
M. S.; Campbell, I. B. J. Org. Chem. 2003, 68, 3844–
3848.
In conclusion, we have studied the kinetic resolution of
different N-protected b-aminoalcohols in the presence of
a solution phase or a solid-supported N-40pyridinyl-a-
methyl proline derived catalyst. The trifluoroacetyl
group represents the most promising N-protecting
group, giving the highest selectivities with all alcohols
tested. The advantages of this protecting group are in
its quantitative formation and also in its ease of cleavage
without loss of enantioselectivity. We envisage further
use of the trifluoroacetyl group for the kinetic resolution
of a wide library of structurally different aminoalcohols.
Acknowledgement
18. Pelotier, B.; Priem, G.; Campbell, I. B.; Macdonald, S. J.
F.; Anson, M. S. Synlett 2003, 679–683.
This work was supported by a grant from the Marie
Curie European Commission (HPMI-CT-1999-00021).
19. Procedure for trifluoroacetamide cleavage: N-(CF3CO)-
protected (1R,2S)-(+)-cis-1-amino-2-indanol 2f (0.05
mmol) was stirred at room temperature in 1.5 ml of a
2 M ammonia in methanol solution until completion
(2 days). Solvent was removed and (1R,2S)-(+)-cis-1-
amino-2-indanol was purified on a silica gel column (ethyl
acetate then methanol). The optical rotation of recovered
References and notes
1. Kagan, H. B.; Fiaud, J. C. Top. Stereochem. 1988, 18,
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2. For reviews, see: (a) Williams, J. M. J.; Parker, R. J.; Neri,
C. In Enzyme Catalysis in Organic Synthesis; Drauz, K.,
20
alcohol is ½aꢁD +62.2 (c 0.4, chloroform). In the literature
22
(99% ee/GLC, Aldrich): ½aꢁD +63 (c 0.2, chloroform).