A. P. Dobbs et al. / Tetrahedron Letters 49 (2008) 827–831
831
Thus, hydrogenation of the 2-ethoxycarbonyl 6-methyl-
tetrahydropyridine 21 simultaneously reduced the double
bond and removed the N-benzyl protecting group to give
the corresponding piperidine 23 in 87% yield, which upon
treatment with acid gave the trans-6-methyl pipecolic acid
24 in 83% yield and 53% overall yield from 20. Alterna-
tively, treatment of 2-carboxyethyl ester 6-trifluoromethyl-
tetrahydropyridine 22 with a catalytic quantity of osmium
tetroxide and excess NMO gave the dihydroxylated piper-
idine 25 in 83% yield, with the cis addition of the diol
occurring exclusively from the bottom face of the molecule
(the same face as the CF3 substituent). The diol could be
stored and purified more readily as the diacetate 26.
In conclusion, we have shown that the silyl-Prins and
aza-silyl-Prins reactions may be employed for the prepara-
tion of 6-CF3-substituted dihydropyrans and 6-CF3-substi-
tuted tetrahydropyridines, and that these products may be
further elaborated to a number of saturated heterocycles,
including pipecolate derivatives. The use of the trifluoro-
methyl group in the starting materials has also raised a
number of interesting mechanistic questions, and these
are the subject of ongoing investigations, the results of
which will be reported in due course.
(Swansea) for mass spectral data. We also wish to thank
´
Dr. Sebastien Guesne for helpful discussions.
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We are grateful to Glaxo SmithKline (CASE award to
R.J.P.) and the EPSRC (DTA award to R.J.P.) for funding
and the EPSRC National Mass Spectrometry Service