D. A. Klumpp et al. / Tetrahedron Letters 42 (2001) 5821–5823
5823
improvement over a similar AlCl3-catalyzed reaction,
which gives low yields of aryl-piperidines.2 It is pro-
posed that the 1,2,3,6-tetrahydropyridines are proto-
nated twice in CF3SO3H to generate reactive, dicationic
electrophiles.14 While the 1,4-dications are preferred
over the isomeric 1,3-dications, substitution by alkyl or
aryl groups can reverse this trend.
5. Weissman, J.; Trevor, A.; Chibs, K.; Peterson, L. A.;
Caldera, P.; Castagnoli, Jr., N. J. Med. Chem. 1985, 28,
997.
6. Klumpp, D. A.; Garza, M.; Jones, A.; Mendoza, S. J.
Org. Chem. 1999, 64, 6702.
7. Reaction conditions: 0.2 g of the tetrahydropyridine is
dissolved in 1.0 mL of C6H6, and 3.0 mL of CF3SO3H is
slowly added. After stirring for at least 4 hours at 25°C,
the mixture is poured over ice, made basic with NaOH,
and extracted with CHCl3. The resulting organic solution
is dried with MgSO4 and concentrated to give the
Acknowledgements
1
product. All products were fully characterized by H and
Financial support of the National Institutes of Health
(SO6GM53933-0251) is gratefully acknowledged. The
helpful assistance of Mr. Siufu Lau is also noted.
13C NMR, GCMS, and high resolution mass spectrome-
try. CF3SO3H can be quantitatively recycled, see: Booth,
B. L.; El-Fekky, T. A. J. Chem. Soc., Perkin 1 1979,
2441.
8. (a) Olah, G. A.; Prakash, G. K. S.; Sommer, J.
Superacids; Wiley: New York, NY, 1985; (b) Saito, S.;
Saito, S.-i.; Ohwada, T.; Shudo, K. Chem. Pharm. Bull.
1991, 39, 2718.
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10. 0.05 g of 3 is reacted with 1.0 g TfOD for 18 h.
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12. N-Methyl-3,3-diphenylpiperidine (12): mp 38–40°C; 1H
NMR (300 MHz, CDCl3) l, ppm: 1.62 (m, 2H), 2.32 (m,
2H), 2.35 (s, 3H), 2.46 (m, 2H), 2.90 (m, 2H), 7.18 (m,
4H), 7.28–7.37 (m, 6H). 13C NMR (125 MHz, CDCl3) l,
ppm: 22.5, 34.8, 46.5, 46.6, 56.2, 65.6, 125.7, 127.6, 128.1,
147.7. HRMS calcd for C18H21N 251.1674, found
251.1668. N-Methyl-cis-(3-benzyl-4-phenyl)piperidine (13):
1H NMR (300 MHz, CDCl3) l, ppm: 0.80–0.90 (m, 1H),
1.47–1.65 (m, 4H), 1.81–1.90 (m, 1H), 2.1 (s, 3H), 2.4 (m,
1H), 2.7 (m, 1H), 2.8 (m, 1H), 3.5 (m, 1H), 7.05–7.30 (m,
10H). 13C NMR (125 MHz, CDCl3) l, ppm: 25.3, 29.34,
36.7, 46.6, 56.2, 57.1, 61.2, 126.1, 126.2, 127.9, 128.0,
128.5, 128.6, 143.5, 143.7. HRMS calcd for C19H23N
265.1830, found 265.1828.
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.