R. G. Bhat et al. / Tetrahedron Letters 45 (2004) 7983–7985
7985
Deblocking of the Poc groupwas achieved by treatment
with tetrathiomolybdate 2 (CH3CN, rt, 1–2.5h) under
neutral and nonhydrolytic conditions in almost quanti-
tative yields.
protected products were purified by column chromato-
graphy on silica gel.
Deprotection of the propargyloxycarbonyl (Poc) group:
A general procedure. To a solution of the propargyl
urethane (carbamate) (4mmol) in acetonitrile (5mL),
benzyltriethylammonium tetrathiomolybdate 2 (1.2equiv,
4.8mmol) was added. The Poc groupwas deblocked
completely within 2–2.5h. The deprotection was moni-
tored by TLC. After the reaction, the solvent was
Under dealkylation and Poc deprotection conditions,
other functionalities present in the substrate were unaf-
fected and we did not observe formation of any side
products due to ring scission. Generally, the debenzyl-
ation was more rapid than other dealkylations. From
the table it is clear that the selectivities for N-dealkyla-
tion followed the order benzyl > allyl > isoprop-
yl > methyl. This can be explained on the basis of the
electrophilicity of the carbon at the alkyl chain.
removed and the residue was taken upin CH Cl2 (3mL)
2
and diethyl ether (10mL) and the solution was filtered
through a pad of Celite. The filtrate was concentrated
and the product was purified by column chromatogra-
phy on silica gel to give the secondary amine in almost
quantitative yield.
A typical dealkylation takes 0.2–2h with stirring at
room temperature or 0.2–1.5h at reflux. As the proparg-
yloxycarbonyl (Poc) groupis stable to acidic and basic
conditions and its deblocking is achieved by treatment
with tetrathiomolybdate 2 under neutral conditions,
the reactivity of the Poc grouphas been explored further
as an orthogonal protecting group in organic synthesis.
We synthesised three carbonates (Table 1: 18, 21 and 24)
starting from N-benzyl 4-hydroxy piperidine. Treatment
of compounds 18, 21 and 24 with propargyl chlorofor-
mate 1 (CHCl3, À23°C) resulted in the formation of
the corresponding N-Poc piperidine carbonates 19, 22
and 25, respectively, in excellent yields. Further treat-
ment of 19, 22 and 25 with tetrathiomolybdate 2,
(CH3CN, rt, 2–2.5h) resulted in the formation of the
corresponding secondary amines 20, 23 and 26, respec-
tively, in excellent yields. The carbonate protecting
groups (Cbz, Alloc, Moc) were unaffected under the
reaction conditions (Table 1).
Acknowledgements
We thank DRDO, New Delhi, for financial support of
this investigation.
References and notes
1. Brewster, J. H.; Eliel, E. L. In Organic Reactions; Adams,
R., Ed.; John Wiley and Sons: New York, 1953; Vol. VII,
p142.
2. Olofoson, R. A.; Schur, R. C.; Bunes, L.; Pepe, J. P.
Tetrahedron Lett. 1977, 1567.
3. Cooley, J. H.; Evain, E. J. Synthesis 1989, 1, and
references cited therein.
4. Campbell, A. L.; Pilipauskas, D. R.; Khanna, I. K.;
Rhodes, R. A. Tetrahedron Lett. 1987, 28, 2331.
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In conclusion, we have developed a new, efficient and
mild methodology for dealkylation of tertiary amines.
This method provides an excellent protocol for N-dealk-
ylation in general, and N-debenzylation in particular
without using any strong base or acid. The propargyl-
oxycarbonyl groupwas deblocked under neutral, mild
and nonhydrolytic conditions. Orthogonality of the
Poc groupcan be exlpoited for a wide range of
functionalities.
A typical procedure for N-dealkylation: To the tertiary
amine (4mmol) in dry chloroform (5mL) cooled to
À23°C, propargyl chloroformate 1 (5mmol, 0.5mL)
was added dropwise under inert atmosphere (N2). The
intermediate Poc-amine salt (X) was either allowed to
warm to room temperature with stirring (2–2.5h) or
the reaction mixture was refluxed for 0.2–1.5h. The
dealkylation was monitored by TLC. The reaction mix-
ture was diluted with diethyl ether (30mL) and was
washed with water and brine solution. The organic layer
was dried over anhydrous sodium sulfate. The N-Poc
10. To a stirred solution of diphosgene (1.2mL, 10mmol) in
dry diethyl ether (30mL), activated charcoal (0.05g) was
added and the suspension was stirred overnight at room
temperature (25°C). The solution was cooled to 0°C and
propargyl alcohol (0.9mL, 15mmol) in dry diethyl ether
(10mL) was added dropwise. The resultant solution was
stirred for 12h and filtered. The ethereal layer was distilled
under reduced pressure and the liquid obtained was used
without further purification.
11. (a) Sinha, S.; Ilankumaran, P.; Chandrasekaran, S.
Tetrahedron Lett. 1999, 40, 771; (b) Sridhar, P. R.;
Chandrasekaran, S. Org. Lett. 2002, 4, 4731.