Sustainable, mild and efficient p-methoxybenzyl ether deprotections utilizing catalytic DDQ

Article abstract of DOI:10.1016/j.tet.2014.07.003

A procedure for the selective deprotection of p-methoxybenzyl ethers using catalytic amounts of DDQ and of sodium nitrite, with oxygen as the terminal oxidant, is reported.

Full text of DOI:10.1016/j.tet.2014.07.003

Tetrahedron 70 (2014) 7380e7387
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Sustainable, mild and efficient p-methoxybenzyl ether
deprotections utilizing catalytic DDQ
,
Katie Walsh a, Helen F. Sneddon b, Christopher J. Moody a
*
a School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK
b Green Chemistry Performance Unit, GlaxoSmithKline R&D Ltd, Medicines Research Centre,
Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 14 May 2014
Received in revised form 26 June 2014
Accepted 1 July 2014
A procedure for the selective deprotection of p-methoxybenzyl ethers using catalytic amounts of DDQ
and of sodium nitrite, with oxygen as the terminal oxidant, is reported.
Ó 2014 Elsevier Ltd. All rights reserved.
Available online 5 July 2014
Dedicated to the memory of Professor Sandy
McKillop, an outstanding organic chemist
Keywords:
Deprotection
Oxidation
Quinone
1. Introduction
electron transfer with formation of p-anisaldehyde as a by-
product. However, the use of this oxidant in stoichiometric
p-Methoxybenzyl (PMB) ethers are one of the most widely used
hydroxyl protecting groups in synthetic organic chemistry, mainly
owing to their stability, easy application and selective deprotection
in the presence of unsubstituted benzyl ethers. They have been
used in the synthesis of many natural products,1,2 for example,
discodermolide,3 a marine natural product with antitumour activ-
ity currently in clinical trial. A variety of conditions can be
employed to remove PMB ethers, including Brønsted or Lewis acids,
such as triflic acid,4 cerium(III) triflate and chloride,5,6 silver(I)
hexafluoroantimonate7 and zirconium(IV) chloride.8 In addition to
acidic conditions, they can also be removed by hydrogenolysis9 or
oxidation.10,11
One of the most popular methods for deprotection of PMB
ethers is oxidative deprotection using 2,3-dichloro-5,6-dicyano-p-
benzoquinone (DDQ).12,13 This widely used oxidant has been
successfully employed in the synthesis of several natural prod-
ucts,14 such as (þ)-indicanone,15 and operates by via single-
amounts results in large quantities of hydroquinone by-product
that make purification difficult. In addition, DDQ is moderately
expensive with a cost of $515/mol (at March 2014) and there are
some toxicity concerns associated with its use; the compound has
an LD50 of 82 mg/kg and can release HCN fumes on contact with
water. However, this effective organic oxidant is widely used in
organic synthesis as a result of its good selectivity, wide applica-
bility and availability.
The use of catalytic DDQ alongside a benign terminal oxidant
is a more efficient and sustainable alternative. Previous attempts
at oxidations using catalytic quantities of DDQ can be found
in the literature. However, these processes have resorted to using
18
several equivalents of metal salts, such as Mn(OAc)3,16,17 MnO2
and FeCl3
19
in order to reoxidize the hydroquinone.
However, there are examples where nitrite co-oxidants, such as
tert-butyl nitrite20 or sodium nitrite21 are employed. These re-
agents are used in catalytic amounts to generate nitric oxide (NO)
in situ, in the presence of acetic acid,22,23 which is then oxidized
to nitrogen dioxide. This species is able to reoxidize the hydro-
quinone, regenerating DDQ. Two examples are shown in
Scheme 1.
* Corresponding
author.
E-mail
address:
c.j.moody@nottingham.ac.uk
(C.J. Moody).
http://dx.doi.org/10.1016/j.tet.2014.07.003
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

K. Walsh et al. / Tetrahedron 70 (2014) 7380e7387
7381
Table 1 (continued )
Entry
Product
DDQ/mol % Yield/%
12
13
1.5
90c
90c
,f
1.5
1.5
14
92e
a
Reaction conditions: PMB-protected alcohol (1 mmol), DDQ, NaNO2
(2ꢀDDQ mol %), HOAc, O2, rt, 18 h.
b
Crude product purified by flash chromatography.
Crude product washed with NaHSO3, no purification necessary.
Yields in brackets correspond to those attained using flash chromatography as
c
d
Scheme 1. Literature examples of sodium nitrite and tert-butyl nitrite for catalytic
DDQ oxidations.
opposed to NaHSO3 workup.
e
Reaction time was 60 h.
Reaction carried out on 0.35 mmol.
f
As a result we sought to optimize a procedure in which oxidative
deprotection of PMB ethers could be successfully carried out under
more ‘green’ and environmentally sustainable conditions, using
catalytic DDQ, catalytic sodium nitrite and oxygen as the terminal
oxidant.
methods; flash chromatography or washing with saturated aque-
ous sodium bisulfite solution to remove the p-anisaldehyde by-
product. Both methods of extraction worked equally well, al-
though the ability to obtain the desired product without the need
for flash chromatography is highly desirable and produces less
waste. This often proved beneficial since some products were dif-
ficult to separate from the anisaldehyde by-product by chroma-
tography. Catalyst loadings were also kept low for all examples,
with most able to achieve complete conversion with just 1.5 mol %
DDQ, somewhat lower catalyst loadings than previously reported
uses of DDQ. It should be noted that the reactions perform best
when carried out under oxygen atmosphere; significantly longer
reaction times and reduced yields were observed when the re-
actions were carried out under air.
2. Results and discussion
A selection of protected alcohols was synthesized and subjected
to oxidative deprotection (Table 1). The reactions were found to
work best with a 1 M solution of the substrate in acetic acid. Di-
lution of the mixture with a co-solvent resulted in longer reaction
times. Upon completion the product could be extracted by two
Table 1
p-Methoxybenzyl ether deprotections using catalytic DDQa
The results show that a variety of alcohols containing different
functionality can be deprotected successfully. Surprisingly, when
deprotecting cyclohex-2-enol (entry 3) the resulting allylic al-
cohol did not oxidize further to the ketone, as reported in
a previous literature example when using manganese acetate to
regenerate the DDQ.16 However, with cinnamyl alcohol (entry 4)
the product was immediately oxidized under the reaction con-
ditions, generating cinnamaldehyde. Removal of p-methox-
ybenzyl protecting groups on phenols, both electron rich and
electron deficient (entry 7 and 8), proved unsuccessful with re-
covery of the starting material. A small selection of alcohols
containing additional orthogonal protecting groups was also
subjected to the conditions. These include benzyl ether (entry
10), silyl ethers (entries 11 and 12), ethoxy methoxy (EOM) (entry
13) and an acetate ester (entry 14), all of which could be selec-
tively deprotected in good yield.
Entry
1
Product
DDQ/mol % Yield/%
5
2
93b
2
3
77c (72)d
5
81b
4
5
5
86b
84b
3.5
3. Conclusion
6
7
1.5
5
91c
An efficient, green and sustainable method for the deprotection
of p-methoxybenzyl (PMB) ethers, using only catalytic amounts of
DDQ has been developed. Good yields could be obtained with
a variety of protected alcohols with low catalyst loadings. Chro-
matography to purify the product was unnecessary in most cases as
reactions could be washed with saturated aqueous sodium bisulfite
in order to remove the anisaldehyde by-product. Deprotections
were also found to be selective against other alcohol protecting
groups, such as benzyl ether, silyl ethers, EOM and an acetate ester.
No
reactione
8
9
5
No
reaction
4. Experimental section
4.1. General information
2.5
87b
10
11
1.5
1.5
81c(83)d
89c
Commercially available compounds were purchased and used
without purification unless otherwise stated. All anhydrous
(continued on next page)

7382
K. Walsh et al. / Tetrahedron 70 (2014) 7380e7387
solvents were used as supplied, except tetrahydrofuran and
dichloromethane that were freshly distilled according to standard
procedures, although drying of solvents was not necessary in the
catalytic procedures listed. Reactions were routinely carried out
under an atmosphere of argon unless otherwise noted and glass-
ware was oven-dried before use. Light petroleum refers to the
fraction with bp 40e60 ꢁC. Ether refers to diethyl ether. Analytical
thin layer chromatography was carried out on aluminium-backed
plates coated with silica gel, and visualized under UV light at 254
and/or 360 nm and/or by chemical staining. Flash chromatography
was carried out using silica gel, with the eluent specified. Infrared
spectra were recorded using an FT-IR spectrometer over the range
4000e600 cmꢂ1. NMR spectra were recorded at 400 MHz (1H fre-
quency, 100 MHz 13C frequency). Chemical shifts are quoted in parts
per million (ppm), and are referenced to residual H in the deuter-
ated solvent as the internal standard. Coupling constants, J, are
quoted in hertz (Hz). In the 13C NMR spectra, signals corresponding
to CH, CH2, or CH3 groups are assigned from DEPT. Mass spectra
were recorded on a time-of-flight mass spectrometer using elec-
trospray ionization (ESI), or an EI magnetic sector instrument.
and washed with saturated aqueous sodium bisulfite solution
(3ꢀ20 mL), dried over magnesium sulfate and evaporated under
reduced pressure.
4.6. Preparation of PMB ethers
4.6.1. 1-Methoxy-4-(oct-3-yn-1-yloxy)methylbenzene.
The title compound was synthesized following general pro-
cedure method A from 3-octyn-1-ol (1.08 mL, 7.5 mmol), sodium
hydride (60% in oil, 335 mg, 8.25 mmol) and p-methoxybenzyl
chloride (1.02 mL, 7.5 mmol) in THF (10 mL) at room temperature
for 20 h. Purification by flash chromatography (0:1 to 1:19 diethyl
ether/light petroleum) gave the title compound as a colourless oil
(651 mg, 35%). Found: MþNaþ, 269.1520. C16H22O2Naþ requires
269.1517; ymax (ATR)/cmꢂ1 2999, 2932, 2860, 2062, 1613, 1513; dH
(400 MHz; CDCl3) 7.30 (2H, d, J 8.8 Hz, ArH), 6.90 (2H, d, J 8.8 Hz,
ArH), 4.51 (2H, s, CH2), 3.83 (3H, s, OCH3), 3.56 (2H, t, J 7.2 Hz, CH2),
2.48 (2H, tt, J 7.0, 2.4 Hz, CH2), 2.17 (2H, tt, J 7.2, 2.4 Hz, CH2),
1.51e1.39 (4H, m, CH2), 0.93 (3H, t, J 7.2 Hz, CH3); dC (100 MHz;
CDCl3) 159.2 (C), 130.4 (C), 129.3 (CH), 113.4 (CH), 81.4 (C), 76.6 (C),
72.6 (CH2), 68.7 (CH2), 55.3 (CH3), 31.1 (CH2), 21.9 (CH2), 20.2 (CH2),
18.5 (CH2), 13.6 (CH3).
4.2. General procedure method A
To a microwave vial (35 mL) was added sodium hydride (60% in
oil, 8e16 mmol) that was washed with pentane (30 mL) and sus-
pended in THF (10e15 mL) before
a solution of alcohol
(7.5e10 mmol) in THF (2 mL) was added dropwise with stirring. The
mixture was left to stir for 30 min at room temperature before 4-
methoxybenzyl chloride (8e16 mmol) was added. The mixture
was stirred at room temperature under an argon atmosphere for
20 h, then poured into saturated aqueous sodium hydrogen car-
bonate (40 mL), and extracted with ethyl acetate (2ꢀ30 mL). The
organic extracts were washed with brine (40 mL) and dried over
sodium sulfate before being concentrated under reduced pressure.
Purification of the residue was carried out by flash chromatography.
4.6.2. 1-(Hex-5-yn-1-yloxy)methyl-4-methoxybenzene.
The title compound was synthesized following general pro-
cedure method A from 5-hexyn-1-ol (827
hydride (60% in oil, 609 mg, 15 mmol) and p-methoxybenzyl
chloride (1017 L, 7.5 mmol) in THF (10 mL) at room temperature
mL, 7.5 mmol), sodium
4.3. General procedure method B
m
To a microwave vial containing alcohol (7.5e10 mmol) and dii-
sopropylethylamine (9e12 mmol) was added 4-methoxybenzyl
chloride (8e16 mmol), the vial sealed under an atmosphere of ar-
gon, and heated to 130e150 ꢁC for 3 h. The mixture was poured into
saturated aqueous sodium hydrogen carbonate (40 mL) and
extracted with ethyl acetate (2ꢀ30 mL). The organic extracts were
washed with brine (40 mL) and dried over sodium sulfate before
being concentrated under reduced pressure. Purification of the
residue was carried out by flash chromatography.
for 20 h. Purification by flash chromatography (0:1 to 1:19 diethyl
ether/light petroleum) gave the title compound as a colourless oil
(651 mg, 35%). Found: MþNaþ, 241.1183. C14H18O2Naþ requires
241.1204; nmax (ATR)/cmꢂ1 3294, 2939, 2862, 2116, 1613, 1513; dH
(400 MHz; CDCl3) 7.28 (2H, d, J 8.8 Hz, ArH), 6.90 (2H, d, J 8.8 Hz,
ArH), 4.45 (2H, s, CH2), 3.83 (3H, s, OCH3), 3.49 (2H, t, J 6.2 Hz, CH2),
2.23 (2H, td, J 6.9, 2.6 Hz, CH2), 1.97 (1H, t, J 2.6 Hz, CH), 1.79e1.72
(2H, m, CH2), 1.68e1.61 (2H, m, CH2); dC (100 MHz; CDCl3) 159.1 (C),
130.7 (C), 129.2 (CH), 113.8 (CH), 84.8 (C), 72.5 (CH2), 69.4 (CH2),
68.4 (CH), 55.3 (CH3), 28.7 (CH2), 25.3 (CH2), 18.2 (CH2). Data
recorded match literature.24
4.4. General procedure method C
To
a Reacti-vial (Thermo Scientific) containing the 4-
4.6.3. 1-(Cyclohex-2-en-1-yloxy)methyl-4-methoxybenzene.
methoxybenzyl protected alcohol (1 mmol) were added sodium
nitrite (3e10 mol %), glacial acetic acid (1 mL) and 2,3-dichloro-5,6-
dicyano-1,4-benzoquinone (DDQ) (1.5e5 mol %). The resulting
mixture was stirred at room temperature under an atmosphere of
oxygen for 18 h. The solution was then evaporated under reduced
pressure and the residue purified by flash chromatography.
The title compound was synthesized following general pro-
cedure method A using cyclohex-2-enol (736 mL, 7.5 mmol), sodium
4.5. General procedure method D
hydride (60% in oil, 335 mg, 8.25 mmol) and p-methoxybenzyl
chloride (1.02 mL, 7.5 mmol) in THF (10 mL) at room temperature
for 20 h. Purification by flash chromatography (0:1 to 1:19 diethyl
ether/light petroleum) gave the title compound as a colourless oil
(296 mg, 18%). Found: MþNaþ, 241.1195. C14H18O2Naþ requires
241.1204; ymax (ATR)/cmꢂ1 3008, 2939, 2838, 1612, 1586, 1513; dH
(400 MHz; CDCl3) 7.31 (2H, d, J 8.7 Hz, ArH), 6.90 (2H, d, J 8.7 Hz,
ArH), 5.89 (1H, dtd, J 10.1, 3.5, 1.3 Hz, CH), 5.84e5.80 (1H, m, CH),
To a Reacti-vial (Thermo Scientific) containing 4-methoxybenzyl
protected alcohol (1 mmol) were added sodium nitrite
(3e10 mol %), glacial acetic acid (1 mL) and 2,3-dichloro-5,6-
dicyano-1,4-benzoquinone (1.5e5 mol %). The resulting mixture
was stirred at room temperature under an atmosphere of oxygen
for 18 h. The solution was then diluted with ethyl acetate (30 mL)

K. Walsh et al. / Tetrahedron 70 (2014) 7380e7387
7383
4.57 (1H, d, J 11.5 Hz, CH2), 4.51 (1H, d, J 11.5 Hz, CH2), 3.96 (1H, br s,
CH), 3.83 (3H, s, OCH3), 2.12e2.05 (1H, m, CH2), 2.01e1.95 (1H, m,
CH2), 1.89e1.72 (3H, m, CH2), 1.62e1.55 (1H, m, CH2); dC (100 MHz;
CDCl3) 159.1 (C), 131.2 (C), 130.8 (CH), 129.2 (CH), 127.9 (CH), 113.8
(CH), 71.9 (CH), 69.7 (CH2), 55.3 (CH3), 28.4 (CH2), 25.3 (CH2), 19.3
(CH2). Data recorded match literature.25
CH), 2.21 (1H, d, J 11.9 Hz, CH), 1.70e1.63 (2H, m, CH2), 1.41e1.26
(2H, m, CH2), 1.03e0.83 (3H, m, CH, CH2), 0.96 (3H, d, J 6.7 Hz, CH3),
0.91 (3H, d, J 7.3 Hz, CH3), 0.73 (3H, d, J 6.9 Hz, CH3); dC (100 MHz;
CDCl3) 159.0 (C), 131.3 (C), 129.4 (CH), 113.7 (CH), 78.4 (CH), 70.1
(CH2), 55.3 (CH3), 48.3 (CH), 40.3 (CH2), 34.6 (CH2), 31.6 (CH), 25.5
(CH), 23.3 (CH2), 22.4 (CH3), 21.0 (CH3), 16.1 (CH3).
4.6.4. 1-(Cinnamyloxy)methyl-4-methoxybenzene.
4.6.7. 2-(4-Methoxybenzyloxy)benzonitrile.
Thetitlecompound wassynthesizedfollowing generalprocedure
method A from cinnamyl alcohol (967
(60% in oil, 609 mg, 15 mmol) and 4-methoxybenzyl chloride
(1.02 L, 7.5 mmol) in THF (10 mL) at room temperature for 20 h.
mL, 7.5 mmol), sodium hydride
The title compound was synthesized following general pro-
cedure method B from 2-hydroxybenzonitrile (1.19 g, 10 mmol), 4-
methoxybenzyl chloride (1.02 mL, 10 mmol), sodium iodide
(112 mg,10 mol %) and diisopropylethylamine (2.10 mL,12 mmol) at
140 ꢁC for 3 h. Purification by flash chromatography (2:3 ethyl ac-
etate/light petroleum) gave the title compound as a colourless solid
(442 mg, 17%). Found: MþNaþ, 262.0817. C15H13NO2Naþ requires
262.0844; ymax (ATR)/cmꢂ1 3007, 2937, 2839, 2231, 1613, 1599; dH
(400 MHz; CDCl3) 7.60 (1H, dd, J 7.5, 1.6 Hz, ArH), 7.52 (1H, ddd, J
8.3, 7.5, 1.6 Hz, ArH), 7.41 (2H, d, J 8.7 Hz, ArH), 7.05e7.01 (2H, m,
ArH), 6.95 (2H, d, J 8.7 Hz, ArH), 5.18 (2H, s, CH2), 3.85 (3H, s, OCH3);
dC (100 MHz; CDCl3) 160.4 (C), 159.6 (C), 134.2 (CH), 133.9 (CH),
128.8 (CH), 127.7 (C), 121.0 (CH), 116.5 (C), 114.1 (CH), 113.1 (CH),
102.5 (C), 70.5 (CH2), 55.3 (CH3). Data recorded match literature.27
m
Purification by flash chromatography (0:1 to 1:9 ethyl acetate/light
petroleum) gave the title compound as a yellow oil (869 mg, 46%).
Found: MþNaþ, 277.1183. C17H18O2Naþ requires 277.1204; ymax
(ATR)/cmꢂ1 3027, 2836, 1612, 1586, 1513, 1450; dH (400 MHz; CDCl3)
7.44e7.41 (2H, m, ArH), 7.37e7.32 (4H, m, ArH), 7.29e7.25 (1H, m,
ArH),6.93(2H, d, J8.7Hz, ArH), 6.65 (1H, d, J 15.9Hz, CH), 6.36(1H, dt,
J15.9, 6.1Hz, CH), 4.54(2H, s, CH2), 4.20(2H, d, J6.1Hz, CH2), 3.83(3H,
s, CH3); dC (100 MHz; CDCl3) 159.3 (C),136.8 (C),132.5 (CH),130.4 (C),
129.5 (CH), 128.6 (CH),127.7 (CH),126.5 (CH), 126.2 (CH), 113.8 (CH),
71.9 (CH2), 70.5 (CH2), 55.3 (CH3). Data recorded match literature.26
4.6.5. 3-(4-Methoxybenzyloxy)propanenitrile.
4.6.8. 1,3-Dimethoxy-5-(4-methoxybenzyloxy)benzene.
The title compound was synthesized following general pro-
cedure method B from 3-hydroxypropanenitrile (684 mL, 10 mmol),
4-methoxybenzyl chloride (1.36 mL, 10 mmol) and diisopropyle-
thylamine (2.10 mL, 12 mmol) at 130 ꢁC for 3 h. Purification by flash
chromatography (0:1 to 1:19 diethyl ether/light petroleum) gave
the title compound as a colourless oil (891 mg, 47%). Found: MþNaþ,
214.0845. C11H13NO2Naþ requires 214.0844; ymax (ATR)/cmꢂ1 3003,
2936, 2872, 2251, 1613, 1585; dH (400 MHz; CDCl3) 7.30 (2H, d, J
8.8 Hz, ArH), 6.92 (2H, d, J 8.8 Hz, ArH), 4.54 (2H, s, CH2), 3.83 (3H, s,
CH3), 3.68 (2H, t, J 6.4 Hz, CH2), 2.62 (2H, t, J 6.4 Hz, CH2); dC
(100 MHz; CDCl3) 159.5 (C), 129.4 (CH), 129.3 (C), 117.8 (C), 114.0
(CH), 73.0 (CH2), 64.3 (CH2), 55.3 (CH3), 18.9 (CH2).
To a flask containing caesium carbonate (4.89 g, 15 mmol) in
dimethylformamide (20 mL) were added 3,5-dimethoxyphenol
(2.31 g, 15 mmol) and p-methoxybenzyl chloride (1.36 mL,
10 mmol) and the mixture stirred at 20 ꢁC for 24 h. The mixture was
diluted with ethyl acetate (40 mL) and washed with lithium chloride
(5%; 3ꢀ40 mL) and brine (40 mL) before being dried over magne-
sium sulfate and evaporated under reduced pressure to give the
crude product as a yellow oil. Purification by flash chromatography
(1:4 ethyl acetate/light petroleum) gave the title compound as a col-
ourless solid (971 mg, 35%). Found: MþNaþ, 297.1085. C16H18O4Naþ
requires 297.1103; ymax (CHCl3)/cmꢂ1 3010, 2961, 2840, 1602, 1515,
1463; dH (400 MHz; CDCl3) 7.38 (2H, d, J 8.6 Hz, ArH), 6.94 (2H, d, J
8.6 Hz, ArH), 6.20 (2H, d, J 2.2 Hz, ArH), 6.13 (1H, t, J 2.2 Hz, ArH), 4.97
(2H, s, CH2), 3.84 (3H, s, OCH3), 3.79 (6H, s, OCH3); dC (100 MHz;
CDCl3) 161.5 (C),160.8 (C),159.5 (C),129.4 (CH),129.0 (C),114.0 (CH),
93.8 (CH), 93.2 (CH), 69.9 (CH2), 55.3 (CH3), 55.3 (CH3).
4.6.6. 1-((1S,2R,5S)-2-Isopropyl-5-methylcyclohexyloxy)methyl-4-
methoxybenzene.
The title compound was synthesized following general pro-
cedure method B from (1S,2R,5S)-menthol (1.17 g, 10 mmol), 4-
methoxybenzyl chloride (1.02 mL, 10 mmol), sodium iodide
(112 mg,10 mol %) and diisopropylethylamine (2.10 mL,12 mmol) at
140 ꢁC for 3 h. Purification by flash chromatography (1:99 to 1:49
ethyl acetate/light petroleum) gave the title compound as a colour-
less oil (366 mg, 18%). Found: MþNaþ, 299.1964. C18H28O2Naþ re-
quires 299.1987; ymax (ATR)/cmꢂ1 2953, 2922, 2868, 1613, 1586,
1513; dH (400 MHz; CDCl3) 7.29 (2H, d, J 8.8 Hz, ArH), 6.89 (2H, d, J
8.8 Hz, ArH), 4.61 (1H, d, J 11.1 Hz, CH2), 4.35 (1H, d, J 11.1 Hz, CH2),
3.82 (3H, s, OCH3), 3.17 (1H, td, J 10.4, 4.3 Hz, CH), 2.34e2.29 (1H, m,
4.6.9. 1,10-Bis(4-methoxybenzyloxy)decane.
The title compound was synthesized following general pro-
cedure method B from 1,10-decandiol (8.71 g, 50 mmol), 4-

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K. Walsh et al. / Tetrahedron 70 (2014) 7380e7387
methoxybenzyl chloride (6.78 mL, 50 mmol) and diisopropyle-
thylamine (10.5 mL, 60 mmol) at 140 ꢁC for 3 h. Purification by flash
chromatography (0:1 to 1:1 diethyl ether/light petroleum) gave the
title compound as a colourless crystalline solid (4.48 g, 30%); mp
41e43 ꢁC. Found: MþNaþ, 437.2667. C26H38O4Naþ requires
437.2668; ymax (ATR)/cmꢂ1 3007, 2934, 2857, 1612, 1586, 1513; dH
(400 MHz; CDCl3) 7.29 (4H, d, J 8.8 Hz, ArH), 6.91 (4H, d, J 8.8 Hz,
ArH), 4.46 (4H, s, CH2), 3.83 (6H, s, OCH3), 3.46 (4H, t, J 6.7 Hz, CH2),
1.66e1.58 (4H, m, CH2), 1.39e1.27 (12H, m, CH2); dC (100 MHz;
CDCl3) 159.1 (C), 130.9 (C), 129.5 (CH), 113.8 (CH), 72.5 (CH2), 70.3
(CH2), 55.3 (CH3), 29.8 (CH2), 29.6 (CH2), 29.5 (CH2), 26.2 (CH2).
(40 mL) and extracted with ethyl acetate (2ꢀ30 mL). The organic
extracts were washed with brine (40 mL) and dried over magne-
sium sulfate before being evaporated under reduced pressure. The
crude product was purified by elution through a pad of silica to give
the title compound as a colourless oil (1.58 g, 96%). Found: MþNaþ,
555.3259. C34H48O3SiNaþ requires 555.3270; ymax (ATR)/cmꢂ1
3072, 3008, 2933, 2857, 1612, 1587; dH (400 MHz; CDCl3) 7.71e7.69
(4H, m, ArH), 7.48e7.39 (6H, m, ArH), 7.29 (2H, d, J 8.8 Hz, ArH), 6.92
(2H, d, J 8.8 Hz, ArH), 4.48 (2H, s, CH2), 3.84 (3H, s, OCH3), 3.70 (2H,
t, J 6.6 Hz, CH2), 3.48 (2H, t, J 6.6 Hz, CH2), 1.66e1.57 (4H, m, CH2),
1.42e1.27 (12H, m, CH2),1.10 (9H, s, CH3); dC (100 MHz; CDCl3) 159.1
(C), 135.6 (CH), 134.2 (C), 130.9 (C), 129.5 (CH), 129.2 (CH), 127.5
(CH), 113.8 (CH), 72.5 (CH2), 70.3 (CH2), 64.0 (CH2), 55.3 (CH3), 32.6
(CH2), 29.8 (CH2), 29.6 (CH2), 29.6 (CH2), 29.5 (CH2), 29.4 (CH2), 26.9
(CH3), 26.3 (CH2), 25.8 (CH2), 19.3 (C).
4.6.10. 10-(4-Methoxybenzyloxy)decan-1-ol.
4. 6.13. tert-Butyl(10-(4-methoxybenzyloxy)decyloxy)
dimethylsilane.
The title compound was synthesized following general pro-
cedure method B from 1,10-decandiol (8.71 g, 50 mmol), 4-
methoxybenzyl chloride (6.78 mL, 50 mmol) and diisopropyle-
thylamine (10.5 mL, 60 mmol) at 140 ꢁC for 3 h. Purification by flash
chromatography (0:1 to 1:1 diethyl ether/light petroleum) gave the
title compound as a colourless crystalline solid (4.48 g, 30%); mp
44e45 ꢁC. Found: MþNaþ, 317.2093. C18H30O3Naþ requires
317.2093; ymax (ATR)/cmꢂ1 3623, 3009, 2932, 2857, 1612, 1586; dH
(400 MHz; CDCl3) 7.28 (2H, d, J 8.8 Hz, ArH), 6.90 (2H, d, J 8.8 Hz,
ArH), 4.45 (2H, s, CH2), 3.82 (3H, s, OCH3), 3.65 (2H, t, J 6.7 Hz, CH2),
3.45 (2H, t, J 6.7 Hz, CH2), 1.65e1.54 (4H, m, CH2), 1.50 (1H, s, OH),
1.38e1.27 (12H, m, CH2); dC (100 MHz; CDCl3) 159.1 (C), 130.8 (C),
129.2 (CH), 113.7 (CH), 72.5 (CH2), 70.2 (CH2), 63.1 (CH2), 55.3 (CH3),
30.8 (CH2), 29.8 (CH2), 29.5 (CH2), 29.5 (CH2), 29.4 (CH2), 29.4 (CH2),
26.2 (CH2), 25.7 (CH2).
To
a flask containing 10-(4-methoxybenzyloxy)decan-1-ol
(900 mg, 3.06 mmol) and imidazole (230 mg, 3.37 mmol) in
dichloromethane (10 mL) was added tert-butyldimethylsilyl chlo-
ride (866 mL, 3.37 mmol) and the solution stirred under argon for
20 h at room temperature. The mixture was poured in water
(40 mL) and extracted with ethyl acetate (2ꢀ30 mL). The organic
extracts were washed with brine (40 mL) and dried over magne-
sium sulfate before being evaporated under reduced pressure. The
crude product was purified by elution through a pad of silica to give
the title compound as a colourless oil (1.07 g, 86%). Found: MþNaþ,
431.2941. C24H44O2SiNaþ requires 431.2957; ymax (ATR)/cmꢂ1 2929,
2855, 1613, 1586, 1513, 1463; dH (400 MHz; CDCl3) 7.29 (2H, d, J
8.7 Hz, ArH), 6.90 (2H, d, J 8.7 Hz, ArH), 4.45 (2H, s, CH2), 3.83 (3H, s,
OCH3), 3.62 (2H, t, J 6.6 Hz, CH2), 3.45 (2H, t, J 6.6 Hz, CH2),1.63e1.58
(2H, m, CH2), 1.54e1.51 (2H, m, CH2), 1.38e1.27 (12H, m, CH2), 0.92
(9H, s, CH3), 0.07 (6H, s, CH3); dC (100 MHz; CDCl3) 159.1 (C), 130.8
(C), 129.2 (CH), 113.7 (CH), 72.5 (CH2), 70.2 (CH2), 63.6 (CH2), 55.3
(CH3), 32.9 (CH2), 29.8 (CH2), 29.6 (CH2), 29.6 (CH2), 29.5 (CH2), 29.4
(CH2), 26.2 (CH2), 26.0 (CH3), 25.8 (CH2), 18.4 (C), ꢂ5.3 (CH3).
4.6.11. 1-Methoxy-4-((3-benzyloxypropoxy)methyl)-benzene.
The title compound was synthesized following general pro-
cedure method
A from 3-benzyloxy-1-propanol (1.19 mL,
7.5 mmol), sodium hydride (60% in oil, 335 mg, 8.25 mmol) and 4-
methoxybenzyl chloride (1.02 mL, 7.5 mmol) in THF (10 mL) at
room temperature for 20 h. Purification by flash chromatography
(0:1 to 1:9 diethyl ether/light petroleum) gave the title compound as
4.6.14. 1-(10-(Ethoxymethoxydecyloxy)methyl)-4-methoxybenzene.
a
C
colourless oil (1.21 g, 57%). Found: MþNaþ, 309.1460.
18H22O3Naþ requires 309.1467; ymax (ATR)/cmꢂ1 3031, 2858, 1612,
1586, 1513, 1454; dH (400 MHz; CDCl3) 7.39e7.30 (5H, m, ArH), 7.27
(2H, d, J 8.7 Hz, ArH), 6.90 (2H, d, J 8.7 Hz, ArH), 4.53 (2H, s, CH2),
4.46 (2H, s, CH2), 3.83 (3H, s, OCH3), 3.61 (2H, t, J 6.4 Hz, CH2), 3.59
(2H, t, J 6.4 Hz, CH2), 1.95 (2H, pentet, J 6.4 Hz, CH2); dC (100 MHz;
CDCl3) 159.2 (C), 138.6 (C), 130.7 (C), 129.3 (CH), 128.4 (CH), 127.7
(CH), 127.5 (CH), 113.8 (CH), 73.0 (CH2), 72.7 (CH2), 67.4 (CH2), 67.0
(CH2), 55.3 (CH3), 30.2 (CH2).
To a flask containing a suspension of sodium hydride (60% in oil,
160 mg, 4 mmol) in tetrahydrofuran (5 mL) was added 10-(4-
methoxybenzyloxy)decan-1-ol (588 mg, 2 mmol) in tetrahydrofu-
ran (3 mL) and the resulting mixture stirred for 30 min. Chlor-
omethyl ethylether (372 mL, 4 mmol) was added dropwise before
stirring continued for 24 h at room temperature. The mixture was
quenched with aqueous ammonium hydroxide (35%; 30 mL) and
extracted into ethyl acetate (2ꢀ20 mL). The organic layers were
combined and washed with brine (30 mL) before being dried over
magnesium sulfate and concentrated under reduced pressure to
give the crude product as a yellow oil. Purification by flash chro-
matography (3:17 ethyl acetate/light petroleum) gave the title
compound as a colourless oil (141 mg, 20%). Found: MþNaþ,
375.2510. C21H36O4Naþ requires 375.2511; ymax (ATR)/cmꢂ1 2933,
2857, 1612, 1513, 1465, 1363; dH (400 MHz; CDCl3) 7.28 (2H, d, J
8.7 Hz, ArH), 6.90 (2H, d, J 8.7 Hz, ArH), 4.69 (2H, s, CH2), 4.45 (2H, s,
CH2), 3.83 (3H, s, OCH3), 3.62 (2H, q, J 7.0 Hz, CH2), 3.55 (2H, t, J
4. 6.12. tert-Butyl(10-(4-methoxybenzyloxy)decyloxy)
diphenylsilane.
To a flask containing 10-((4-methoxybenzyl)oxy)decan-1-ol
(900 mg, 3.06 mmol) and imidazole (230 mg, 3.37 mmol) in
dichloromethane (10 mL) was added tert-butyldiphenylsilyl chlo-
ride (875
mL, 3.37 mmol) and the solution stirred under argon for
20 h at room temperature. The mixture was poured in water

K. Walsh et al. / Tetrahedron 70 (2014) 7380e7387
7385
6.6 Hz, CH2), 3.45 (2H, t, J 6.6 Hz, CH2), 1.65e1.56 (4H, m, CH2),
1.40e1.28 (12H, m, CH2), 1.24 (3H, t, J 7.0 Hz, CH3); dC (100 MHz;
CDCl3) 159.1 (C), 130.8 (C), 129.2 (CH), 113.7 (CH), 95.1 (CH2), 72.5
(CH2), 70.2 (CH2), 67.9 (CH2), 63.1 (CH2), 55.3 (CH3), 29.8 (CH2), 29.8
(CH2), 29.5 (CH2), 29.5 (CH2), 29.4 (CH2), 26.2 (CH2), 15.2 (CH3);
2ꢀCH2s not observed.
2.7 Hz, CH), 1.75e1.60 (4H, m, CH2), 1.52 (1H, s, OH); dC (100 MHz;
CDCl3) 84.3 (C), 68.5 (CH), 62.4 (CH2), 31.7 (CH2), 24.7 (CH2), 18.2
(CH2). Data recorded match literature.28
4.7.3. Cyclohex-2-enol.
4.6.15. 10-(4-Methoxybenzyloxy)decyl acetate.
The title compound was synthesized following general pro-
cedure method
C
from 1-(cyclohex-2-en-1-yloxy)methyl-4-
methoxybenzene (218 mg, 1 mmol), sodium nitrite (7 mg,
10 mol %), glacial acetic acid (1 mL) and 2,3-dichloro-5,6-dicyano-
1,4-benzoquinone (11 mg, 5 mol %). Purification by flash chroma-
tography (0:1 to 1:9 diethyl ether/light petroleum) gave the title
compound as a colourless oil (79 mg, 81%); ymax (ATR)/cmꢂ1
3550e3200, 3024, 2936, 1650, 1435, 1286; dH (400 MHz; CDCl3)
5.85 (1H, dtd, J 10.0, 3.7, 1.0 Hz, CH), 5.77 (1H, ddd, J 10.0, 4.8, 1.9 Hz,
CH), 4.21 (1H, br s, CH), 2.10e1.84 (3H, m, CH2), 1.80e1.55 (4H, m,
CH2); OH not observed; dC (100 MHz; CDCl3) 130.6 (CH), 129.9 (CH),
65.5 (CH), 32.0 (CH2), 25.0 (CH2), 18.9 (CH2). Data recorded match
literature.29
To
(588 mg, 2 mmol) in pyridine (5 mL) was added acetic anhydride
(373 L, 4 mmol) and the resulting solution stirred for 36 h at room
a flask containing 10-(4-methoxybenzyloxy)decan-1-ol
m
temperature. The mixture was quenched with aqueous hydro-
chloric acid (1 M; 30 mL) and extracted into ethyl acetate
(2ꢀ20 mL). The organic layer was washed with saturated aqueous
sodium hydrogen carbonate solution (30 mL), followed by further
aqueous hydrochloric acid (1 M; 30 mL), before being dried over
magnesium sulfate and concentrated under reduced pressure to
give the crude product as a yellow oil. Purification by flash chro-
matography (1:4 ethyl acetate/light petroleum) gave the title
compound as a colourless oil (322 mg, 48%). Found: MþNaþ,
359.2194. C20H32O4Naþ requires 359.2198; ymax (ATR)/cmꢂ1 2933,
2857, 1728, 1612, 1513, 1465; dH (400 MHz; CDCl3) 7.29 (2H, d, J
8.7 Hz, ArH), 6.90 (2H, d, J 8.7 Hz, ArH), 4.45 (2H, s, CH2), 4.07 (2H, t,
J 6.9 Hz, CH2), 3.83 (3H, s, OCH3), 3.45 (2H, t, J 6.7 Hz, CH2), 2.07 (3H,
s, CH3), 1.65e1.58 (4H, m, CH2), 1.40e1.27 (12H, m, CH2); dC
(100 MHz; CDCl3) 171.3 (CHO), 159.1 (C), 130.8 (C), 129.2 (CH), 113.7
(CH), 72.5 (CH2), 70.2 (CH2), 64.7 (CH2), 55.3 (CH3), 29.8 (CH2), 29.5
(CH2), 29.5 (CH2), 29.4 (CH2), 29.2 (CH2), 28.6 (CH2), 26.2 (CH2), 25.9
(CH2), 21.0 (CH3).
4.7.4. Cinnamaldehyde.
The title compound was synthesized following general pro-
cedure method C from 1-(cinnamyloxy)methyl-4-methoxybenzene
(254 mg, 1 mmol), sodium nitrite (7 mg, 10 mol %), glacial acetic
acid (1 mL) and DDQ (11 mg, 5 mol %). Purification by flash chro-
matography (10e20% ethyl acetate/light petroleum) gave the title
compound as a colourless oil (113 mg, 86%); dH (400 MHz; CDCl3)
9.75 (1H, d, J 7.8 Hz, CHO), 7.62e7.59 (2H, m, ArH), 7.52 (1H, d, J
15.9 Hz, CH), 7.49e7.45 (3H, m, ArH), 6.76 (1H, dd, J 15.9, 7.8 Hz,
CH); dC (100 MHz; CDCl3) 193.7 (CHO), 152.8 (CH), 134.0 (C), 131.3
(CH), 129.1 (CH), 128.5 (CH), 128.3 (CH). Data recorded match
literature.30
4.7. Deprotection reactions
4.7.1. 3-Octyn-1-ol.
4.7.5. 3-Hydroxypropanenitrile.
The title compound was synthesized following general pro-
cedure method C from 1-methoxy-4-(oct-3-yn-1-yloxy)methyl-
benzene (246 mg, 1 mmol), sodium nitrite (7 mg, 10 mol %), glacial
acetic acid (1 mL) and DDQ (11 mg, 5 mol %). Purification by flash
chromatography (0:1 to 1:4 diethyl ether/light petroleum) gave the
title compound as a colourless oil (117 mg, 93%). Found: MþNaþ,
149.0929. C8H14ONaþ requires 149.0942; ymax (ATR)/cmꢂ1
3550e3200, 2873, 2230, 2071,1744,1725; dH (400 MHz; CDCl3) 3.69
(2H, t, J 6.2 Hz, CH2), 2.45 (2H, tt, J 6.2, 2.4 Hz, CH2), 2.19 (2H, tt, J 7.0,
2.4 Hz, CH2), 1.84 (1H, br s, OH), 1.53e1.38 (4H, m, CH2), 0.93 (3H, t, J
7.0 Hz, CH3); dC (100 MHz; CDCl3) 82.7 (C), 76.2 (C), 61.4 (CH2), 31.1
(CH2), 23.2 (CH2), 22.0 (CH2), 18.4 (CH2), 13.6 (CH3).
The title compound was synthesized following general pro-
cedure method
C from 3-(4-methoxybenzyloxy)propanenitrile
(191 mg, 1 mmol), sodium nitrite (5 mg, 7 mol %), glacial acetic acid
(1 mL) and DDQ (8 mg, 3.5 mol %). Purification by flash chroma-
tography (1:1 ethyl acetate/light petroleum) gave the title com-
pound as
a
colourless oil (60 mg, 84%); ymax (ATR)/cmꢂ1
3600e3300, 2961, 2899, 2253,1474,1413; dH (400 MHz; CDCl3) 3.92
(2H, t, J 6.1 Hz, CH2), 2.64 (2H, t, J 6.1 Hz, CH2), 2.27 (1H, br s, OH); dC
(100 MHz; CDCl3) 118.2 (C), 57.8 (CH2), 21.5 (CH2).
4.7.6. (1S,2R,5S)-Menthol.
4.7.2. 5-Hexyn-1-ol.
The title compound was synthesized following general pro-
cedure
method
C
from
1-(hex-5-yn-1-yloxy)methyl-4-
methoxybenzene (218 mg, 1 mmol), sodium nitrite (3 mg,
4 mol %), glacial acetic acid (1 mL) and DDQ (5 mg, 2 mol %) gave the
title compound as a colourless oil (71 mg, 72%); ymax (ATR)/cmꢂ1
3550e3200, 2943, 2116, 1434, 1062, 990; dH (400 MHz; CDCl3) 3.70
(2H, t, J 6.3 Hz, CH2), 2.26 (2H, td, J 6.8, 2.7 Hz, CH2), 1.98 (1H, t, J
The title compound was synthesized following general pro-
cedure
methylcyclohexyloxy)methyl-4-methoxybenzene
1 mmol), sodium nitrite (2 mg, 3 mol %), glacial acetic acid (1 mL)
method
D
from
1-((1S,2R,5S)-2-isopropyl-5-
(276 mg,

7386
K. Walsh et al. / Tetrahedron 70 (2014) 7380e7387
and DDQ (3 mg, 1.5 mol %) gave the title compound as a pale yellow
solid (142 mg, 91%); mp 39e41 ꢁC (lit.31 mp 40e41.5 ꢁC). Found:
MþNaþ, 179.1411. C10H20ONaþ requires 179.1412; ymax (ATR)/cmꢂ1
3607, 3008, 2959, 2926, 2850, 1456; dH (400 MHz; CDCl3) 3.43 (1H,
td, J 10.3, 4.3 Hz, CH), 2.23e2.15 (1H, m, CH), 2.02e1.96 (1H, m,
CH2), 1.71e1.61 (2H, m, CH2), 1.51e1.40 (1H, m, CH), 1.13 (1H, ddt, J
12.9, 10.3, 3.1 Hz, CH), 1.05e0.85 (3H, m, CH2), 0.95 (3H, t, J 6.7 Hz,
CH3), 0.93 (3H, t, J 6.7 Hz, CH3), 0.83 (3H, d, J 6.9 Hz, CH3); OH not
observed; dC (100 MHz; CDCl3) 71.6 (CH), 50.2 (CH), 45.1 (CH2), 34.5
(CH2), 31.6 (CH), 25.9 (CH), 23.2 (CH2), 22.2 (CH3), 21.0 (CH3), 16.1
(CH3). Data recorded match literature.32
4.7.10. 10-(tert-Butyldimethylsilyloxy)decan-1-ol.
The title compound was synthesized following general pro-
cedure method
D from tert-butyl(10-(4-methoxybenzyloxy)
decyl)dimethylsilane (409 mg, 1 mmol), sodium nitrite (2 mg,
3 mol %), glacial acetic acid (1 mL) and DDQ (3 mg, 1.5 mol %)
gave the title compound as an orange oil (259 mg, 90%). Found:
MþNaþ, 311.2366. C16H36SiO2Naþ requires 311.2382; ymax (ATR)/
cmꢂ1 3622, 3011, 2931, 2857, 1471, 1464; dH (400 MHz; CDCl3)
3.64 (4H, dt, J 19.1, 6.6 Hz, CH2), 1.61e1.50 (4H, m, CH2), 1.39e1.29
(12H, m, CH2), 0.92 (9H, s, CH3), 0.08 (6H, s, CH3); OH not ob-
served; dC (100 MHz; CDCl3) 63.4 (CH2), 63.1 (CH2), 32.9 (CH2),
32.8 (CH2), 29.5 (CH2), 29.4 (CH2), 29.4 (CH2), 26.0 (CH3), 25.8
(CH2), 25.7 (CH2), 25.6 (CH2), 18.4 (C), ꢂ5.2 (CH3). Data recorded
match literature.36
4.7.7. 1,10-Decanediol.
The title compound was synthesized following general pro-
cedure method
C from 1,10-bis((4-methoxybenzyl)oxy)decane
(414 mg, 1 mmol), sodium nitrite (4 mg, 5 mol %), glacial acetic acid
(1 mL) and DDQ (6 mg, 2.5 mol %). Purification by flash chroma-
tography (1:1 diethyl ether/light petroleum) gave the title com-
pound as a colourless oil (151 mg, 87%); mp 69e71 ꢁC (lit.33 mp
70e71 ꢁC). Found: MþNaþ, 197.1917. C10H22O2Naþ requires
197.1917; ymax (ATR)/cmꢂ1 3623, 3010, 2931, 2857, 1465, 1389; dH
(400 MHz; CDCl3) 3.66 (4H, t, J 6.6 Hz, CH2), 1.58 (4H, quintet, J
7.2 Hz, CH2), 1.45 (2H, s, OH), 1.38e1.32 (12H, m, CH2); dC (100 MHz;
CDCl3) 63.1 (CH2), 32.8 (CH2), 29.5 (CH2), 29.4 (CH2), 25.7 (CH2).
4.7.11. 10-(Ethoxymethoxy)decan-1-ol.
The title compound was synthesized following general pro-
cedure method D from 1-((10-(ethoxymethoxy)decyloxy)methyl)-
4-methoxybenzene (123 mg, 0.35 mmol), sodium nitrite (1 mg,
3 mol %), glacial acetic acid (350 mL) and DDQ (1 mg, 1.5 mol %) gave
the title compound as a yellow oil (72 mg, 90%). Found: MþNaþ,
255.1918.
C
13H28O3Naþ requires 255.1936; ymax (ATR)/cmꢂ1
4.7.8. 3-Benzyloxy-1-propanol.
3500e3300, 2926, 1465, 1387, 1260; dH (400 MHz; CDCl3) 4.69 (2H,
s, CH2), 3.65 (2H, t, J 6.6 Hz, CH2), 3.61 (2H, q, J 7.1 Hz, CH2), 3.54 (2H,
t, J 6.6 Hz, CH2), 1.61e1.54 (4H, m, CH2), 1.40e1.28 (12H, m, CH2),
1.24 (3H, t, J 7.1 Hz, CH3); OH not observed; dC (100 MHz; CDCl3)
95.0 (CH2), 67.9 (CH2), 63.1 (CH2), 63.0 (CH2), 32.8 (CH2), 29.7 (CH2),
29.5 (CH2), 29.5 (CH2), 29.4 (CH2), 29.4 (CH2), 26.2 (CH2), 25.7 (CH2),
15.2 (CH3).
The title compound was synthesized following general pro-
cedure method D from 1-methoxy-4-(3-(phenylmethoxy)propoxy)
methylbenzene (286 mg, 1 mmol), sodium nitrite (2 mg, 3 mol %),
glacial acetic acid (1 mL) and DDQ (3 mg, 1.5 mol %) gave the title
compound as a colourless oil (133 mg, 81%). Found: MþNaþ,
4.7.12. 1-Hydroxydecyl acetate.
189.0878.
C
10H14O2Naþ requires 189.0891; ymax (ATR)/cmꢂ1
3600e3200, 3031, 2944, 2865, 1496, 1454; dH (400 MHz; CDCl3)
7.40e7.29 (5H, m, ArH), 4.55 (2H, s, CH2), 3.81 (2H, t, J 5.8 Hz, CH2),
3.69 (2H, t, J 5.8 Hz, CH2), 2.27 (1H, br s, OH), 1.90 (2H, quintet, J
5.8 Hz, CH2); dC (100 MHz; CDCl3) 138.1 (C), 128.5 (CH), 127.7 (CH),
127.7 (CH), 73.3 (CH2), 69.4 (CH2), 61.9 (CH2), 32.1 (CH2). Data
recorded match literature.34
The title compound was synthesized following general pro-
cedure method D from 10-(4-methoxybenzyloxy)decyl acetate
(322 mg, 0.95 mmol), sodium nitrite (2 mg, 3 mol %), glacial acetic
acid (1 mL) and DDQ (3 mg, 1.5 mol %) gave the title compound as
a yellow oil (198 mg, 92%). Found: MþNaþ, 239.1608. C12H24O3Naþ
requires 239.1623; ymax (ATR)/cmꢂ1 3600e3300, 2928, 1739, 1601,
1366,1242; dH (400 MHz; CDCl3) 4.07 (2H, t, J 6.7 Hz, CH2), 3.65 (2H,
t, J 6.7 Hz, CH2), 2.06 (3H, s, CH3), 1.66e1.54 (4H, m, CH2), 1.40e1.29
(12H, m, CH2); OH not observed; dC (100 MHz; CDCl3) 171.3 (C), 64.7
(CH2), 63.0 (CH2), 32.8 (CH2), 29.5 (CH2), 29.4 (CH2), 29.4 (CH2), 29.2
(CH2), 28.6 (CH2), 25.9 (CH2), 25.7 (CH2), 21.0 (CH3). Data recorded
match literature.37
4.7.9. 10-(tert-Butyldiphenylsilyloxy)decan-1-ol.
The title compound was synthesized following general pro-
cedure method
D from tert-butyl(10-(4-methoxybenzyl)oxy)
decyloxydiphenylsilane (533 mg, 1 mmol), sodium nitrite (2 mg,
3 mol %), glacial acetic acid (1 mL) and DDQ (3 mg, 1.5 mol %) gave
the title compound as a colourless oil (366 mg, 89%). Found:
MþNaþ, 435.2692. C26H40SiO2Naþ requires 435.2695; ymax (ATR)/
cmꢂ1 3550e3300, 3070, 2929, 2856, 1471, 1427; dH (400 MHz;
CDCl3) 7.70 (4H, dd, J 7.6, 1.5 Hz, ArH), 7.45e7.38 (6H, m, ArH), 3.68
(4H, td, J 6.6, 2.6 Hz, CH2), 1.62e1.55 (4H, m, CH2), 1.38e1.27 (12H,
m, CH2), 1.08 (9H, s, CH3); OH not observed; dC (100 MHz; CDCl3)
135.6 (CH), 134.2 (C), 129.5 (CH), 127.6 (CH), 64.0 (CH2), 63.1 (CH2),
32.8 (CH2), 32.6 (CH2), 29.6 (CH2), 29.5 (CH2), 29.4 (CH2), 29.4
(CH2), 26.9 (CH3), 25.8 (CH2), 25.7 (CH2), 19.2 (C). Data recorded
match literature.35
Acknowledgements
We thank the Engineering and Physical Sciences Research
Council and GlaxoSmithKline for an Industrial CASE award (to
K.W.).
References and notes
1. Evans, D. A.; Gage, J. R.; Leighton, J. L. J. Am. Chem. Soc. 1992, 114, 9434e9453.
2. Burke, S. D.; Letourneau, J. J.; Matulenko, M. A. Tetrahedron Lett. 1999, 40, 9e12.
3. Caron, S.; Dugger, R. W.; Ruggeri, S. G.; Ragan, J. A.; Ripin, D. H. B. Chem. Rev.
2006, 106, 2943e2989.

K. Walsh et al. / Tetrahedron 70 (2014) 7380e7387
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