tert-Butyl Ethers: Renaissance of an Alcohol ProtectingGroup
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2H), 2.04 (s, 3H), 3.33 (t, JH,H ¼6.4 Hz, 2H), 4.05 (t, JH,H
6.6 Hz, 2H); 13C NMR: d¼20.9 (CH3), 25.7 (CH2), 25.9
(CH2), 27.5 (CH3), 28.5 (CH2), 30.5 (CH2), 61.3 (CH2), 64.5
(CH2), 72.3 (C), 171.1(C).
¼
Experimental Section
General Remarks
(6-tert-Butoxyhexyloxymethyl)-benzene (3b): 1,6-Hexane-
diol was protected as the mono-benzyl ether followinga known
procedure.[21] The isolated mono-ether was treated with Boc2O
in the presence of Mg(ClO4)2 to give 3b. 1H NMR: d¼1.18 (s,
9H), 1.30–1.40 (m, 4H), 1.50–1.55 (m, 2H), 1.60–1.65 (m,
2H), 3.32 (t, JH,H ¼6.8 Hz, 2H), 3.47 (t, JH,H ¼6.6 Hz, 2H),
4.50 (s, 2H), 7.25–7.35 (m, 5H); 13C NMR: d¼26.1 (CH2),
26.1 (CH2), 27.6 (CH3), 29.7 (CH2), 30.6 (CH2), 61.5 (CH2),
70.4 (CH2), 72.4 (C), 72.8 (CH2), 127.4 (CH), 127.6 (CH),
128.3 (CH), 138.7 (C).
The 1H and 13C NMR spectra were recorded at 400 or 300 MHz
and 100 or 75 MHz, respectively. The chemical shifts (d) are
given in ppm relative to the signals of the solvent (CHCl3) or
TMS. Couplingconstants are given in Hz. Carbon types were
determined by DEPT 13C NMR experiments. The following
abbreviations are used to indicate the multiplicity: s (singlet),
d (doublet), t (triplet), q (quartet), m (multiplet), bs (broad sig-
nal). The purification of the reaction products was carried out
by flash chromatography on silica gel (230–400 mesh).
(6-tert-Butoxyhexyloxy)-triisopropylsilane (3c): 1,6-Hexa-
nediol was protected as the mono-silyl ether[22] followinga
known procedure. The isolated mono-ether was treated with
Boc2O in the presence of Mg(ClO4)2 to give 3c. 1H NMR: d¼
1.05–1.10 (m, 21H), 1.18 (s, 9H), 1.35–1.40 (m, 4H), 1.50–
1.60 (m, 4H), 3.33 (t, JH,H ¼6.8 Hz, 2H), 3.67 (t, JH,H ¼6.6 Hz,
2H); 13C NMR: d¼12.0 (CH), 18.0 (CH3), 25.8 (CH2), 26.1
(CH2), 27.6 (CH3), 30.7 (CH2), 33.0 (CH2), 61.6 (CH2), 63.4
(CH2), 72.3 (C).
Materials
Commercial grade reagents and solvents were used without
further purification. All reagents were purchased from Aldrich
and used as received.
Preparation ofthe Starting Materials: Synthesis of tert-
Butyl Ethers 1 and 3
1-[(6-tert-Butoxyhexyloxy)methyl]-4-methoxybenzene
(3d): 1,6-Hexanediol was mono-protected as the p-methoxy-
[23]
benzyl ether followinga known procedure.
The isolated
tert-Butyl ethers 1a–c, 1e–k, 1m and 1p–s were prepared from
the correspondingalcohols accordingto the previously report-
ed procedure.[4] 2-Methyl-2-(2-nitroethoxy)-propane (1d), 1-
tert-butoxy-4-methylbenzene (1l), 2-tert-butoxybenzonitrile
(1n) and 4-tert-butoxybenzaldehyde (1o) are commercial prod-
ucts.
mono-ether was treated with Boc2O in the presence of
1
Mg(ClO4)2 to give 3d. H NMR: d¼1.18 (s, 9H), 1.35–1.40
(m, 4H), 1.45–1.55 (m, 2H), 1.55–1.65 (m, 2H), 3.32 (t, JH,H
¼
6.8 Hz, 2H), 3.43 (t, JH,H ¼6.6 Hz, 2H), 3.80 (s, 3H), 4.43 (s,
2H), 6.85–6.90 (m, 2H), 7.25–7.30 (m, 2H); 13C NMR: d¼
26.1 (CH2), 27.5 (CH3), 29.7 (CH2), 30.6 (CH2), 55.2 (CH3),
61.5 (CH2), 70.1 (CH2), 71.4 (C), 72.4 (CH2), 72.5 (CH2),
113.7 (CH), 129.2 (CH), 130.8 (C), 159.1 (C).
2-(6-tert-Butoxyhexyloxy)-tetrahydro-2H-pyran (3e): 1,6-
Hexanediol was mono-protected as the THP ether following
a known procedure.[24] The isolated mono-ether was treated
with Boc2O in the presence of Mg(ClO4)2 to give 3e. 1H
NMR: d¼1.18 (s, 9H), 1.35–1.45 (m, 4H), 1.50–1.65 (m,
8H), 1.70–1.85 (m, 2H), 3.26 (t, JH,H ¼6.6 Hz, 2H), 3.35–3.40
(m, 1H), 3.45–3.55 (m, 1H), 3.70–3.75 (m, 1H), 3.85–3.90
(m, 1H), 4.55–4.60 (m, 1H); 13C NMR: d¼19.6 (CH2), 25.5
(CH2), 26.1 (CH2), 26.1 (CH2), 27.5 (CH3), 29.7 (CH2), 30.6
(CH2), 30.7 (CH2), 61.5 (CH2), 62.2 (CH2), 67.5 (CH2), 72.3
(C), 98.8 (CH).
1-tert-Butoxyoctane[4] (1a) 2-tert-butoxy-octane[4] (1b),
(1S,2R,4R)-2-tert-butoxy-1-isopropyl-4-methylcyclohexane[4]
(1c) 2-tert-butoxy-1,2-diphenylethanone[4] (1e), 1-tert-butoxy-
non-3-ene[4] (1f), (S)-ethyl 2-tert-butoxypropanoate[17] (1h), 1-
tert-butoxybenzene[4] (1i), 1-tert-butoxynaphthalene[4] (1j), 2-
tert-butoxynaphthalene[4] (1k), 1-tert-butoxy-4-methoxyben-
zene[18] (1m) 1-tert-butoxy-4-nitrobenzene[19] (1p), 1-tert-bu-
toxy-4-fluorobenzene[4] (1q), 1-tert-butoxy-3-chlorobenzene[4]
(1r) are completely characterized known compounds. 1H and
13C NMR data for not described previously compounds are giv-
en below.
1
6-tert-Butoxyhexan-1-ol (1g): H NMR: d¼1.15 (s, 9H),
1.30–1.35 (m, 4H), 1.45–1.55 (m, 5H), 3.30 (t, JH,H ¼6.8 Hz,
2H), 3.59 (t, JH,H ¼6.6 Hz, 2H); 13C NMR: d¼25.6 (CH2),
26.0 (CH2), 27.5 (CH3), 30.5 (CH2), 32.6 (CH2), 61.4 (CH2),
62.7 (CH2), 72.4 (C).
1-tert-Butoxy-4-(3-tert-butoxypropyl)-benzene (1s): 1H
NMR: d¼1.18 (s, 9H), 1.55 (s, 9H), 1.75–1.90 (m, 2H), 2.67
(t, JH,H ¼7.8 Hz, 2H), 3.35 (t, JH,H ¼6.5 Hz, 2H), 7.05–7.10
(m, 2H), 7.15–7.20 (m, 2H); 13C NMR: d¼27.5 (CH3), 27.7
(CH3), 31.8 (CH2), 32.0 (CH2), 60.5 (CH2), 72.5 (C), 83.3 (C),
120.9 (CH), 129.2 (CH), 139.7 (C), 149.0 (C).
Cleavage of tert-Butyl Ethers 1 to Alcohols 2
In a two-necked flask equipped with a magnetic stirring bar,
CeCl3 ·7 H2O (1.0 mmol) was heated at 1308C under vac-
uum.[14] After 1 h the stirringwas turned on and the heating
was continued for 1 additional hour. After switchingoff the
heatingand the vacuum pump argon was introduced in the
flask. After cooling, the tert-butyl ether 1 (1.0 mmol), NaI
(1.0 mmol) and 2 mL of anhydrous CH3CN were added to
the dried cerium(III) chloride. The mixture was then heated
at the desired temperature until the TLC analysis revealed
the disappearance of the startingmaterial. The crude reaction
mixture was diluted with water and extracted with Et2O. The
organic layer was separated, dried over MgSO4, filtered and
the solvent was removed by rotary evaporation. The alcohols
tert-Butyl ethers 3a–e were prepared from 1,6-hexanediol
(2g) which was firstly monoprotected to products 4a–e and
then the tert-butyl group was introduced according to the pre-
viously reported procedure.[4]
Acetic Acid 6-tert-Butoxyhexyl Ester (3a): 1,6-Hexanediol
was protected as the mono-acetate followinga known proce-
dure.[20] The isolated mono-ester was treated with Boc2O in
1
the presence of Mg(ClO4)2 to give 3a. H NMR: d¼1.18 (s,
9H), 1.35–1.40 (m, 4H), 1.50–1.55 (m, 2H), 1.60–1.65 (m,
Adv. Synth. Catal. 2006, 348, 905 – 910
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