PAPER
Er(OTf)3-Catalyzed Formation and Cleavage of tert-Butyl Ethers
77
tert-Butoxybenzene (12a)
Yield: 77%; Rf = 0.40 (PE–Et2O, 9:1).
structurally identified by comparison with commercially
available sample. It should be specified that totally depro-
tected products were obtained in the case of Boc- 1H NMR (300 MHz, CDCl3): d = 1.34 [s, 9 H, C(CH3)3], 6.98–7.06
(m, 3 H, HB, HC, HD), 7.07–7.09 (m, 2 H, HA, HE).
MS: m/z = 150 [M]+, 135 [M – Me]+, 94 [M – t-Bu + H]+, 77 [Ph]+.
Tyr(Boc)Ot-Bu (16a).
In conclusion, we have presented here an eco-compatible
method, which permits to protect/deprotect alcohols and
phenols as tert-butyl ethers; thus, fully recovering the us-
age of this important protecting group one of the few ether
stable under commonly used basic conditions. The protec-
1-tert-Butoxy-4-ethylbenzene (13a)
Yield: 72%; Rf = 0.729 (PE–Et2O, 9:1).
1H NMR (300 MHz, CDCl3): d = 1.22 [t, J (CH3,CH2) = 7.61 Hz,
CH3CH2, 3 H], 1.32 [s, 9 H, C(CH3)3], 2.60 [q, J (CH3,CH2) = 7.61
tion step is performed in solvent free conditions at room
Hz CH3CH2, 2 H], 6.90 (ddd, Jortho = 8.26 Hz, Jmeta = 2.18 Hz,
temperature using really catalytic amount of Er(OTf)3.
Moreover, the catalyst is easily recovered from the aque-
ous phase and reused several times without significant
loss of activity. The experiments carried out in order to
understand the reaction mechanism for the formation of
the tert-butyl ethers showed, contrary to the data reported
in literature, that tert-butyl carbocation intermediate can
be assumed coming from the tert-butyl carbonate deriva-
tive which is the kinetic product of the reaction by means
a pathway resembling the one reported by Pope et al.7 The
deprotection step proposed is still highly eco-friendly
since the tert-butyl group is removed from alcohols and
phenols very quickly using MW irradiation and in meth-
anol, which is considered one of the environmentally pref-
erable solvents.8
Jpara = 0.41 Hz, 2 H, HC, HB), 7.079 (ddd, Jortho = 8.26 Hz,
Jmeta = 2.18 Hz, Jpara = 0.41 Hz, 2 H, HA, HD).
MS: m/z = 178 [M]+, 163 [M – Me]+, 122 [M – t-Bu + H]+, 107 [M
– t-Bu – Me + H]+.
1-Bromo-4-tert-butoxybenzene (14a)
Yield: 69%; Rf = 0.77 (PE–Et2O, 9:1).
1H NMR (300 MHz, CDCl3): d = 1.33 [s, 9 H, C(CH3)3], 6.87 (ddd,
Jortho = 10 Hz, Jmeta = 3.26 Hz, Jpara = 2.17 Hz, 2 H, HA, HD), 7.35
(ddd, Jortho = 8.26 Hz, Jmeta = 2.18 Hz, Jpara = 0.41 Hz, 2 H, HC, HB).
MS: m/z = 229 [M]+, 231 (90%, [M + 2]+), 213 [M – Me]+, 172 [M
– t-Bu]+.
1-tert-Butoxy-4-nitrobenzene (15a)
Yield: 45%; Rf = 0.50 (PE–Et2O, 9:1).
1H NMR (300 MHz, CDCl3): d = 1.46 [s, 9 H, C(CH3)3], 7.05 (ddd,
Jortho = 9.35 Hz, 2 H, HA, HD), 8.16 (ddd, Jortho = 9.35 Hz, 2 H, HC,
HB).
1H NMR spectra were recorded on a Bruker WM 300 instrument.
Reactions were monitored by a GC-MS Agilent workstation, con-
sisting of a GC-6890N (30 m RESTEK-5SIL capillary column) and
an 5973N mass detector. MW-assisted reactions were performed in
Synthos 3000 instrument from Anton Paar. TLC analyses were per-
formed using silica plates 60-F264 on alumina, commercially avail-
able from Merck. Liquid Flash chromatography was performed on
a Supelco VERSA FLASH HTFP station on silica cartridges com-
mercially available from Supelco. All solvents were distilled before
using by standard methods. All commercially available chemicals
were used as received. Petroleum ether (PE) used refers to the frac-
tion boiling in the range 30–60 °C.
MS: m/z = 195 [M]+, 180 [M – Me]+, 123 [M – t-Bu + H]+, 57 [t-
Bu]+.
N-Boc-O-tert-Butylmethyl Tyrosinate (16a)
Yield: 55%; Rf = 0.68 (CH2Cl2–MeOH, 98:2).
1H NMR (300 MHz, CDCl3): d (major isomer) = 1.33 [s, 9 H,
C(CH3)3], 1.55 [s, 9 H, C(CH3)3], 3.00–3.10 (m, 2 H, H-2), 3.69 (s,
3 H, CO2CH3), 4.97–4.99 (m, 1 H, H-1), 6.89–7.12 (m, 4 H, Ar),
7.26 (s, 1 H, NH).
MS: m/z = 351 [M]+, 236 [M – NHBoc + H]+, 178 [M – NHBoc –
CO2Me + H]+,107 [MeOC6H4]+.
Formation of tert-Butyl Ethers; General Procedure
The respective phenol or alcohol (2.0 mmol) was dissolved in di-
tert-butyl dicarbonate (2.3 equiv) under mild heating (<40 °C).
Er(OTf)3 (0.10 mmol, 61.40 mg, 5 mol%) was added to the mixture
under N2 atmosphere and the mixture was stirred at r.t. The reaction
was monitored by TLC or GC/MS. On completion, the mixture was
diluted with Et2O (10 mL) and the Et2O layer was washed with H2O
(3 × 10 mL). The organic phase was dried (Na2SO4), filtered, and
then evaporated under vacuum. If necessary, the desired product
was purified by flash chromatography. The catalyst was recovered
from the aqueous phases by evaporation under vacuum (Table 3).
1-tert-Butoxy-4-(2-tert-butoxyethyl)-2-methoxybenzene (17a)
Yield: 30%; Rf = 0.45 (PE–Et2O, 8.5:1.5).
1H NMR (300 MHz, CDCl3): d = 1.17 [s, 9 H, CH2OC(CH3)3], 1.33
[s, 9 H, ArOC(CH3)3], 2.77 [t, J (CH2,CH2) = 7.26 Hz, 2 H,
CH2CH2Ot-Bu], 3.54 [t, , J (CH2,CH2) = 7.26 Hz, 2 H, CH2CH2Ot-
Bu], 3.80 (s, 3 H, OCH3), 6.69 (dd, Jortho = 8.07 Hz, Jmeta = 2.02 Hz,
1 H, HC), 6.78 (d, Jmeta = 2.02 Hz, 1 H, HB), 6.90 (d, Jortho = 8.07 Hz,
1 H, HD).
MS: m/z = 280 [M]+, 265 [M – Me]+, 224 [M – t-Bu + H]+, 151 [M
– Ot-Bu + H]+,137 [M – t- Bu – CH2Ot-Bu]+.
2-tert-Butoxybutane (8a)
Yield: 97%.
MS: m/z = 115 [M]+, 101 [M – CHO]+, 57 [t-Bu]+.
4-(2-tert-Butoxyethyl)-2-methoxyphenol (17b)
Yield: 70%; Rf = 0.25 (PE–Et2O, 8.5:1.5).
1H NMR (300 MHz, CDCl3): d = 1.18 [s, 9 H, C(CH3)3], 1.64 (br s,
1 H, OH), 2.75 [t, J (CH2,CH2) = 7.68 Hz, CH2CH2Ot-Bu, 2 H],
3.51 [t, J (CH2,CH2) = 7.68 Hz, CH2CH2Ot-Bu, 2 H], 3.88 (s, 3 H,
OCH3), 6.729 (dd, Jortho = 8.07 Hz, Jmeta = 2.012 Hz, 1 H, HC), 6.76
(d, Jmeta = 2.01 Hz, 1 H, HB), 6.830 (d, Jortho = 8.07 Hz, 1 H, HD).
5-tert-Butoxypent-1-ene (10a)
Yield: 85%; Rf = 0.78 (PE–Et2O, 8:2).
1H NMR (300 MHz, CDCl3): d = 1.185 [s, 9 H, C(CH3)3], 1.48–1.65
(m, 2 H, H-2), 2.08–2.13 (m, 2 H, H3), 3.35 (t, JH-1,H-2 = 6.45 Hz, 2
H, H-1), 4.94–5.05 (m, 2 H, H-5, H-5¢), 5.76–5.96 (m, 1 H, H-4).
MS: m/z = 224 [M]+, 194 [M – OMe]+, 151 [M – Ot-Bu + H]+,137
[M – t-Bu – CH2Ot-Bu]+.
MS: m/z = 142 [M]+, 127 [M – Me]+, 69 [M – Ot-Bu]+, 57 [t-Bu]+.
Synthesis 2011, No. 1, 73–78 © Thieme Stuttgart · New York