4474
D. Ferna´ndez-Forner et al. / Tetrahedron Letters 42 (2001) 4471–4474
amine N-methylbenzylamine has been taken as a model
F.; Loffet, A. Tetrahedron Lett. 1995, 36, 5741–5744; (b)
Thieriet, N.; Go´mez-Mart´ınez, P.; Guibe´, F. Tetrahedron
Lett. 1999, 40, 2505–2508.
for the study of the Alloc removal in solution. Go´mez-
Mart´ınez, P.; Dessolin, M.; Guibe´, F.; Albericio, F. J.
Chem. Soc., Perkin Trans. 1 1999, 2871–2874.
10. General procedure for Alloc removal: In a typical experi-
ment, resin 2 (50 mg, 0.05 mmol) was swelled with
CH2Cl2 (4×30 s) and a 1 or 2 M solution of scavenger (20
or 40 equiv.) in CH2Cl2 (for NaBH3CN experiments,
THF was used as a solvent) was first added under an Ar
atmosphere and stirred for 5 min. Then, a 0.01 M solu-
tion of Pd[PPh3]4 (0.1 equiv.) in CH2Cl2 was added and
the resin was allowed to stir. After 10, 20 or 60 minutes,
depending on the experiment, the solution was drained
off, the resin washed with CH2Cl2 (4×30 s) and the
deprotection procedure was repeated once. Finally, the
resin was washed successively with CH2Cl2 (4×30 s),
DMF (4×30 s), dioxane–water (9:1) (3×1 min), MeOH
(4×1 min), DMF (4×30 s) and CH2Cl2 (4×30 s).
11. (a) Lloyd-Williams, P.; Jou, G.; Albericio, F.; Giralt, E.
Tetrahedron Lett. 1991, 32, 4207–4210; (b) Kates, S. A.;
Sole´, N. A.; Johnson, C. R.; Hudson, D.; Barany, G.;
Albericio, F. Tetrahedron Lett. 1993, 34, 1549–1552; (c)
Salvino, J. M.; Mervic, M.; Mason, H. J.; Kiesow, T.;
Teager, D.; Airey, J.; Labaudiniere, R. J. Org. Chem.
1999, 64, 1823–1830.
6. (a) Jensen, K. J.; Alsina, J.; Songster, M. F.; Va´gner, J.;
Albericio, F.; Barany, G. J. Am. Chem. Soc. 1998, 120,
5441–5452; (b) Alsina, J.; Jensen, K. J.; Albericio, F.;
Barany, G. Chem. Eur. J. 1999, 5, 2787–2795.
7. N-Alloc-4-piperidone. Allyl chloroformate (21 mL, 1.5
equiv.) was added to a solution of 4-piperidone monohy-
drate hydrochloride (20 g, 0.13 mol) and K2CO3 (27 g,
1.5 equiv.) in water (300 mL) at 5°C, and the reaction
mixture was allowed to stir for 1 h at 5°C and for another
additional hour at rt. The aqueous solution was saturated
with NaCl and extracted with diethyl ether (4×100 mL).
The combined organic phases were initially washed with
a cold 5% aqueous NH3 solution and brine, dried over
MgSO4, and evaporated to dryness to give the title
product (23.7 g, quantitative yield), which was used with-
out further purification.
8. 4-Amino-N-Alloc-piperidine. A solution of the above
ketone (10 g, 0.05 mol), NaBH3CN (24 g, 7.6 equiv.) and
ammonium acetate (42 g, 10 equiv.) in dry methanol (500
mL) was heated under reflux for 1 h. Methanol was
removed by evaporation and the residue suspended in 300
mL of H2O. The solution was acidified with 2N HCl to
pH 2 (caution, HCN evolution!!), left to stand 15 min with
agitation and washed with EtOAc (2×100 mL). The
aqueous layer was saturated with K2CO3 and extracted
with EtOAc (3×100 mL). The combined organic phases
were washed with brine, dried over MgSO4, and evapo-
rated to dryness to give the title product (7.2 g, 78%
12. Kunz, H.; Ma¨rz, J. Angew. Chem., Int. Ed. Engl. 1988,
27, 1375–1377.
13. The presence of an acid and even of water has been
postulated to be beneficial for increasing the yields of the
cleavage of allyl esters; see Ref. 11a and Kates, S. A.;
Daniels, S. B.; Albericio, F. Anal. Biochem. 1993, 212,
303–310.
1
14. Dangles, O.; Guibe´, F.; Balavoine, G.; Lavielle, S.; Mar-
quet, A. J. Org. Chem. 1987, 52, 4984–4993.
yield), which was shown to be pure by H NMR.
9. (a) Dessolin, M.; Guillerez, M. G.; Thieriet, N.; Guibe´,
.