LETTER
2-Naphthylmethyl (NAP) as a Versatile Amino Protecting Group
2067
(7) For selected examples of total synthesis using the O-NAP
group see: (a) Xia, J.; Alderfer, J. L.; Piskorz, F.; Matta, K.
L. Chem.–Eur. J. 2001, 7, 356. (b) Inoue, M.; Uehara, H.;
Maruyama, M.; Hirama, M. Org. Lett. 2002, 4, 4551.
(c) Csávás, M.; Borbás, A.; Szilágyi, L.; Lipták, A. Synlett
2002, 887. (d) Yvin, J.-C.; Jamois, F.; Ferrières, V.;
Plusquellec, D. PCT Int. Appl. WO 0157053, 2001; Chem.
Abstr. 2001, 135, 137673.
chemoselectively removed in the presence of a number
of protecting groups and chemical functions including
hydroxyl, alkene, ester, acetal, benzyloxy and N-benzyl
groups.
Acknowledgment
(8) (a) Xia, J.; Abbas, S. A.; Locke, R. D.; Piskorz, C. F.;
Alderfer, J. L.; Matta, K. L. Tetrahedron Lett. 2000, 41,
169. (b) Wright, J. A.; Yu, J.; Spencer, J. B. Tetrahedron
Lett. 2001, 42, 4033.
Financial support of this study by grants from CNRS and the as-
sociation ‘Vaincre les Maladies Lysosomales’ is gratefully ack-
nowledged. G. G. thanks the council of Région Centre and the
CNRS for a fellowship.
(9) Ishihara, K.; Kuroki, Y.; Yamamoto, H. Synlett 1995, 41.
(10) Typical experimental procedure: To a solution of 8b (1.7
g, 2.86 mmol) in a 4:1 mixture of CH2Cl2–MeOH (220 mL)
was added DDQ (1.95 g, 8.59 mmol, 3 equiv) under Ar. The
solution was stirred at r.t. for 2 h. The crude mixture was
evaporated to dryness and then taken into CH2Cl2. The
solution was washed with sat. aq NaHCO3 (5 ×). The organic
layer was dried (MgSO4) and concentrated under reduced
pressure. Purification on silica gel (petroleum ether–EtOAc,
3:2) afforded the secondary amine 9 as a colorless oil (1.08
g, 83%).
References
(1) Greene, T. W.; Wuts, P. G. M. In Protective Groups in
Organic Synthesis, 3rd ed.; Wiley: New York, 1999.
(2) (a) Iminosugars: Recent Insights into their Bioactivity and
Potential as Therapeutic Agents In Current Topics in
Medicinal Chemistry; Martin, O. R.; Compain, P., Eds.;
Bentham: Hilversum Netherlands, 2003, 3, issue 5.
(b) Tezuka, K.; Compain, P.; Martin, O. R. Synlett 2000,
1837. (c) Rambaud, L.; Compain, P.; Martin, O. R.
Tetrahedron: Asymmetry 2001, 12, 1807. (d) Martin, O. R.;
Saavedra, O. M.; Xie, F.; Liu, L.; Picasso, S.; Vogel, P.;
Kizu, H.; Asano, N. Bioorg. Med. Chem. 2001, 9, 1269.
(e) Bordier, A.; Compain, P.; Martin, O. R.; Ikeda, K.;
Asano, N. Tetrahedron: Asymmetry 2003, 14, 47.
(3) (a) Godin, G.; Compain, P.; Masson, G.; Martin, O. R. J.
Org. Chem. 2002, 67, 6960. (b) Masson, G.; Compain, P.;
Martin, O. R. Org. Lett. 2000, 2, 2971.
(4) Cipolla, L.; Palma, A.; La Ferla, B.; Nicotra, F. J. Chem.
Soc., Perkin Trans. 1 2002, 2161.
(5) In our case, N-allyl or N-PMB groups were found to be
partially or totally cleaved during the deprotection of the
acetal function in aq TFA (Scheme 1).
(6) (a) Gaunt, M. J.; Yu, J.; Spencer, J. B. J. Org. Chem. 1998,
63, 4172. (b) Gaunt, M. J.; Boschetti, C. E.; Yu, J.; Spencer,
J. B. Tetrahedron Lett. 1999, 40, 1803.
(11) Iwamura, J.; Hirao, N. Tetrahedron Lett. 1973, 2447.
(12) Compounds 11, 13 and 15 were synthesized by alkylation of
the corresponding secondary amines with 2-bromo-
methylnaphthalene.
Typical experimental procedure: To a solution of N-
benzyl piperazine (510 mg, 2.89 mmol) in anhyd THF (30
mL) was added NaH in oil (60%, 140 mg, 3.5 mmol) at 0 °C.
After 30 min, commercial 2-bromomethylnaphthalene (660
mg, 3 mmol) was added and the mixture was stirred for 24 h
at r.t. The reaction was then quenched with a mixture of
MeOH (5 mL) and ice (10 g). The product was extracted
with CH2Cl2 (50 mL). The organic phase was washed with
sat. aq NaHCO3 (2 × 40 mL), dried (MgSO4) and
concentrated under reduced pressure. Purification on silica
gel (petroleum ether–EtOAc, 95:5) afforded the tertiary
amine 11 (645 mg, 71%).
(13) For oxidative mono-debenzylation of tertiary amines
incorporating two N-benzyl substituents using DDQ or CAN
see: Hungerhoff, B.; Samanta, S. S.; Roels, J.; Metz, P.
Synlett 2000, 77.
Synlett 2003, No. 13, 2065–2067 © Thieme Stuttgart · New York