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CH CN
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1
1
O
O
X
(
(
B)
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9
01; (b) Naik, S.; Gopinath, R.; Patel, B. K. Tetrahedron Lett. 2001, 42, 7679–
R-O-H
R
X
7681; (c) Branco, L. C.; Afonso, C. A. M. Tetrahedron 2001, 57, 4405–4410; (d)
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O
O
O
O
(
e) Miyashita, M.; Yoshikoshi, A.; Grieco, P. A. J. Org. Chem. 1977, 42, 3772–
(
C)
(D)
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Scheme 2. Plausible mechanism of replacement of O-allyl group by alcohol and
thiol nucleophiles.
1
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tion of halonium ion intermediate. Moreover, while working with
NCS in a controlled experiment, we observed the formation of C
(
X = Cl) in the NMR-spectra of the reaction mixture. When the
same reaction was performed on a molecule comprising a basic
nitrogen, for example, 2-aminobutanol, the reaction did not pro-
ceed because the NH group prevented the formation of the halo-
2
nium ion intermediate A (Table 2, entry 14). This observation
also supports the proposed mechanistic pathway.
In summary, we have demonstrated the usefulness of allyl tet-
rahydropyranyl ether (ATHPE) as a new tetrahydropyran protect-
ing agent for alcohols and thiols under neutral conditions. The
tolerance of various sensitive functional groups and mild and neu-
tral conditions are the added advantages over classical THP protec-
tion using dihydropyran. The reagent system may also prove useful
in the protection protocols in polyfunctional molecules (Scheme 2).
Applications of the present protection strategy in carbohydrates
are under progress.
2215; (h) Bongini, A.; Cardillo, G.; Orena, M.; Sandari, S. Synthesis 1979, 618–
620.
14. Mukherjee, D.; Shah, B. A.; Gupta, P.; Taneja, S. C. J. Org. Chem. 2007, 72, 8965–
8968.
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928–7929.
7
1
9. A typical procedure for THP protection with ATHPE using NBS in acetonitrile:
To a solution of ATHPE 100 mg (0.71 mol) and 3-bromopropanol 147 mg
(1.05 mol) in acetonitrile (3 mL/mmol substrate), NBS (1.2 equiv) and
3 2
BF (OEt) ,(1 mol %) were successively added. The reaction mixture was
allowed to stir for 2 h at room temperature, concentrated, extracted in
diethyl ether (10 mL) and washed with saturated sodium bicarbonate solution
(
2 4
10 mL). The organic layer was separated, dried over Na SO , evaporated, and
finally the product was purified by column chromatography on alumina to
afford compound 1 as an oily liquid 132.8 mg (85%).2-(3-Bromopropoxy)-
Acknowledgement
tetrahydro-2H-pyran: 1H NMR (200 MHz, CDCl
): d 4.60 (t, 1H, J = 3.92 Hz),
.41 (m, 2H), 3.50 (m, 4H), 2.13 (m, 2H), 1.51–1.79 (m, 6H); C NMR (125 MHz,
3
13
4
The authors (B.K. and M.A.A.) thank UGC/CSIR, New Delhi for
the award of junior research fellowships.
CDCl
Calcd for C
3
): 99.2, 65.2, 62.6, 33.3, 31.1, 31.0, 25.8, 19.8; ESI-MS (M+Na) = 245; Anal.
15BrO : C, 43.07; H, 6.78. Found; C, 43.17; H, 6.71.
0. A typical procedure for THP protection with ATHPE using I in acetonitrile: To a
solution of ATHPE (100 mg 0.71 mol) and citronellol (147 mg, 1.05 mol) in
acetonitrile (3 mL/mmol substrate), molecular I (1.0 mol %) was added. The
8
H
2
2
2
Supplementary data
2
reaction mixture was allowed to stir for 8 h at room temperature,
concentrated, extracted in diethyl ether (10 mL) and washed successively
with 10% sodium thiosulfate (10 mL), saturated sodium bicarbonate solution
(10 mL) and water (10 mL). The organic layer was separated, dried over
Supplementary data (experimental procedures, characteriza-
1
13
tion data, H and C spectra of the synthesized compounds) asso-
Na
2 4
SO , evaporated, and finally the product was purified by column
chromatography on alumina to afford compound 7 as colourless oily liquid
35.1 mg (80%).2-(3,7-Dimethyloct-6-enyloxy)-tetrahydro-2H-pyran. 1H NMR
200 MHz, CDCl ): d 5.09 (t, 1H, J = 7.01 Hz), 4.58 (t, 1H, J = 3.30 Hz), 3.74–3.91
m, 2H), 3.36–3.53 (m, 2H), 1.97 (m, 2H), 1.54–1.70 (m, 14H), 0.84–0.92 (m,
1
(
(
3
References and notes
1
3
6
3
C
H), C NMR (125 MHz, CDCl
0.7, 29.6, 25.5, 25.4, 24.8, 19.6, 17.5, ESI-MS (M+Na) = 264; Anal. Calcd for
: C, 74.95; H, 11.74. Found; C, 74.84; H, 11.78.
3
): 130.3, 124.8, 98.8, 65.8, 62.1, 39.2, 37.2, 37.0,
1
2
.
.
Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 4th ed.; John
Wiley & Sons: New York, 2007.
For a recent review of protecting groups, see: Jarowicki, K.; Kocienski, P. J.
Chem. Soc., Perkin Trans. 1 2001, 2109–2135.
H O
15 28 2
2
1. (a) Hotha, S.; Kashyap, S. J. Am. Chem. Soc. 2006, 128, 9620–9621; (b) Jose, M. L.;
Cristobal, J. L.; Reid, B. F. J. Org. Chem. 1990, 55, 2997–2998.