Water compatible gold(III)-catalysed synthesis of unsymmetrical ethers from alcohols

Article abstract of DOI:10.1002/chem.200701134

An efficient and broad-scoped method for the preparation of unsymmetrical ethers from alcohols catalysed by the simplest and least expensive gold catalyst, NaAuCl₄, is described for the first time. The procedure enables the etherification of benzylic and tertiary alcohols with moderate to good yields under mild conditions with low catalyst loading. Symmetrical ethers, the usual side products in the etherification of alcohols, were not detected in this case. The formation of the racemic ether from a chiral benzyl alcohol suggests the intermediacy of a carbocation, which has not previously been postulated for gold-catalysed reactions involving alcohols.

Full text of DOI:10.1002/chem.200701134

DOI: 10.1002/chem.200701134
Water Compatible Gold
from Alcohols
ACHTRE(UNG III)-Catalysed Synthesis of Unsymmetrical Ethers
Ana B. Cuenca, Gisela Mancha, Gregorio Asensio,* and Mercedes Medio-Simón[a]
Dedicated to Professor Dr. Juan Fornies on the occasion of his 60th birthday
Abstract: An efficient and broad-
scoped method for the preparation of
unsymmetrical ethers from alcohols
catalysed by the simplest and least ex-
pensive gold catalyst, NaAuCl4, is de-
scribed for the first time. The proce-
dure enables the etherification of ben-
zylic and tertiary alcohols with moder-
ate to good yields under mild condi-
tions with low catalyst loading.
Symmetrical ethers, the usual side
products in the etherification of alco-
hols, were not detected in this case.
The formation of the racemic ether
from a chiral benzyl alcohol suggests
the intermediacy of
a carbocation,
Keywords: alcohols · carbocations ·
which has not previously been postulat-
ed for gold-catalysed reactions involv-
ing alcohols.
gold
· homogeneous catalysis ·
Lewis acids
Introduction
as a result of elegant cascade reactions.[1b] Intermolecular ex-
amples are also known but are less frequent, probably be-
cause of the difficulties in controlling the coordination of
the different reacting species in the metal sphere. Neverthe-
less, and despite the interest of gold as a p Lewis acid, the
exploration of this metal in transformations involving other
functional groups is also attractive. In an attempt to extend
the scope of the gold-assisted addition of oxygenated nucle-
ophiles to triple bonds, surprisingly, we found that the major
product obtained when the couple 1-indanol and phenyl
acetylene were used was the symmetric ether of the alcohol.
We immediately envisaged exploring what we thought could
perhaps be an even more interesting transformation given
the possibility of preparing unsymmetrical ethers by alcohol
dehydration.
Ethers are fundamental compounds in organic chemistry
and are widely used as either fragrance precursors[2] or oxy-
genates in reformulated gasoline.[3] Preparation of this kind
of compound has been developed through a wide variety of
procedures, but not without limitations. The Williamson
ether synthesis represents the most widely used method.
However, it involves converting alcohols into halides or to-
sylates, and in most cases, the use of hard bases is incompat-
ible with other functionalities present in the substrates.[4a,5]
Moreover, high yields are restricted to primary alcohols,
while secondary alcohols give low yields and tertiary alco-
hols tend to mainly give an elimination reaction. Alternative
routes to unsymmetrical ethers arising from alcohols and a
Brçnsted acid catalyst[4b] are often conducted under harsh
For a long time gold has been overlooked as a catalyst; how-
ever, this concept has drastically changed in recent years.
This was probably because of its reluctance to participate as
other late transition metals do in standard catalytic cycles
based on redox principles, such as oxidative addition and re-
ductive elimination. In addition, its ability to act as a Lewis
Acid has been undeservedly disregarded. However, gold cat-
alysis has now emerged as one of the most rapidly growing
sub-disciplines in this field of research. Thus, gold-catalysed
reactions have come to be considered as prominent synthet-
ic methods comprising oxidation, reduction and most com-
monly addition reactions to multiple bonds.[1] With regard to
this last group of reactions, the electrophilic activation of an
alkyne towards the addition of a variety of functional
groups is a complex process that provides a diverse range of
reaction outcomes, the mechanistic rationalisation of which
constitutes an interesting, controversial and active field of
research. Intramolecular versions of this reaction have al-
lowed the construction of very valuable complex molecules
[a] Dr. A. B. Cuenca, G. Mancha, Prof. G. Asensio, Dr. M. Medio-Simón
Departamento de Quimica Organica
Universidad de Valencia
Avda Vicent Andres Estelles s/n (Spain)
Fax : (+34)96-354-4939
E-mail: gregorio.asensio@uv.es
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
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FULL PAPER
conditions with a consequent erosion in yields and the for-
mation of mixtures of three possible products, thus limiting
the utility of the method. Consequently, these approaches
predominantly focus on the preparation of symmetrical light
alkyl ethers. Asophisticated and broad-scoped method for
the preparation of ethers from alcohols has been recently
described. However, and in sharp contrast with the above
simple procedures, the reactants used (nBuLi, Ph2PCl) can
restrict its use in practice.[6] Alternatively, the use of a cata-
lyst based on a transition metal appears to be a promising
method for the etherification of alcohols, even though only
a reduced number of metals have been investigated to date.
In general, the results show prevalence for a broad scope of
benzyl alcohols, although solvolytic conditions are required.
On the other hand, the synthesis of a variety of ethers from
alcohols by using Sn and Zr-containing silicate molecular
sieves[17] has been carried out without having to remove
water. Nonetheless, this method is alcohol-structure depen-
dent because of the nature of the catalyst and the need to
diffuse alcohol within the catalyst channels. Thus, despite
the methods reported, the development of new catalysts
which are readily available, active at low loadings and which
offer a broad scope and selectivity is still an open objective
in the synthesis of ethers from alcohols.
selectivity. Therefore, [Yb
A
Results and Discussion
effective and selective catalyst for the preparation of the p-
methoxybenzyl ethers of primary and secondary alcohols.
On the other hand, FeCl3 catalyses the etherification of al-
We report herein, our findings in the synthesis of unsymmet-
rical ethers from alcohols by using the simplest and least ex-
pensive NaAuCl4 catalyst (Scheme 1). The preparation of
[8]
lylic alcohols and some benzylic alcohols with primary and
secondary aliphatic alcohols. Nonetheless, the method re-
quires a relatively high loading of the catalyst and solvolytic
conditions, and an additional concomitant formation of
elimination side products is observed. The data on the prep-
aration of protected alcohols, such as benzhydrol ethers,
with this same catalyst in the literature are controversial.
While one report indicates that no reaction occurs[8] with
this substrate, a subsequent communication accounts[9] for
good results with no change in the catalyst under milder
conditions. The synthesis of unsymmetrical ethers of secon-
dary benzylic alcohols has also been pursued with other
metals, such as palladium(II).[10] Complexes of this metal,
containing nitrogen and phosphorus bidentate ligands in
conjunction with silver triflate (2 equiv) are selective cata-
lysts for the etherification of secondary benzylic alcohols, al-
though the symmetrical ether is a frequent side product.
Propargylic alcohols have received individual attention in
etherification reactions. The preparation of propargyl ethers
by Lewis acid treatment of alcohols with [Co2(CO)8]-prop-
argyl alcohols[11] has been described. However, the major
drawback of this procedure is that the metal is used in over-
stoichiometric amounts. Alternative catalytic methods which
use a rhenium(V)–oxo complex[12] as an effective catalyst
have been reported to accomplish the etherification of both
internal and terminal propargyl alcohols. Comparatively,
Scheme 1. Gold-catalysed etherification of alcohols.
unsymmetrical ethers from two different alcohols requires
an appropriate catalytic system that is capable of distin-
guishing between two identical functions and developing a
dissimilar role for each partner.
This condition is an essential requisite to control the se-
lectivity in the reaction, otherwise a mixture of the three
possible products is potentially expected. As the catalyst
must select between two similar substrates, then the stronger
the contrast in the components of the alcohol pairs, the
greater the possibility that the catalyst has of choosing one
of them to play a differentiated role. Initially, we tested the
reaction of the highly reactive primary p-methoxybenzyl al-
cohol 1a with the less-reactive aliphatic primary, secondary
and tertiary alcohols 2a–h. In a first series of runs, alcohol
1a was reacted with aliphatic primary alcohols 2a–e
(5 equiv) (Table 1, entries 1–5) and NaAuCl4 (2%) at 708C
for 1 h.
ruthenium was only active with the later substrates.[13]
A
rhenium-based catalyst has also been applied to the etherifi-
cation of benzylic alcohols. In this case, the low valent rhe-
nium(I) catalyst[14] has been seen to be more effective for
primary benzylic alcohols. Conversely, the high-valent rheni-
um–oxo complex[15] (very effective with propargylic alco-
hols) was only active with secondary benzylic alcohols, lead-
ing to the corresponding symmetrical or unsymmetrical
ethers with moderate yields as elimination and dispropor-
tion were significant competitive side reactions.
Aliphatic alcohol was used at a moderately higher con-
centration than benzyl alcohol to direct the reaction towards
the formation of the unsymmetrical ether. Linear (2d and
2e, Table 1, entries 4 and 5) a-branched (2a and 2b, en-
tries 1 and 2) and b-branched (2c, entry 3) primary alcohols
reacted under the above conditions without the use of dehy-
drating agents.
The catalyst was also effective in promoting the reaction
of 1a with the secondary alcohol 2 f (Table 1, entry 6) and
with the tertiary alcohols 2g and 2h (Table 1, entries 7
and 8). Owing to the steric hindrance, however, the catalyst
loading had to be increased (5%) to improve the reaction
rate, as did the excess of aliphatic alcohol (10 equiv) in the
Other than the homogeneous catalysis, the heterogeneous
catalyst has been also developed. For example,
[16]
AlPW12O40 has been shown to be a heterogeneous water
resistant Lewis acid that catalyses the etherification of
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G. Asensio et al.
Table 1. Gold
A
Table 2. GoldACHRTE(UNG III)-catalysed etherification of 1-indanol.
Entry
1
Catalyst[a]
A
Product (yield [%])[b]
À
R OH (2)
Entry
1
Catalyst[a]
A
Product (yield [%])[b]
À
R OH (2)
3aa (80)
3ba (83)
2
3
B
3ab (58)
3ac (60)
2
3
A
A
3bd (47)[c]
3bf (96)
A
4
5
A
A
3ad (61)
3ae (58)
4
A
3bi (86)
6
7
8
B
B
B
3af (71)
[a] Catalyst loading: 2% NaAuCl4 (A), 5% NaAuCl4 (B). [b] Isolated
yield. [c] 10 equiv of ethanol were used.
3ag (76)[c]
3ah (58)[c]
Table 3. GoldACHTREU(NG III)-catalysed etherification of secondary benzyl alcohols.
[a] Catalyst loading: 2% NaAuCl4 (A), 5% NaAuCl4 (B). [b] Isolated
yield. [c] 10 equiv of alcohol 2 were used. Reaction run over 16 h.
Entry
1
Substrate
Ether
Yield [%][a]
56
case of 2g. It is worth mentioning that in our case, and in
sharp contrast with Brçnsted acid catalysis[18] or other prece-
dent methods, the unsymmetrical ether was always the main
product without any contamination of the symmetrical ether
derived from the benzyl alcohol. In addition, the adequate
excess of the aliphatic alcohol 2 used was sufficient to pre-
clude the reaction of alcohol 1a with the water that built up
in the system, thus allowing the reaction to take place with-
out the need for dehydrating agents.
2
3
95[b]
53
The etherification reaction of 1a with 2 f was selected as a
model and further tested with other AuIII and AuI catalysts.
The efficiency found for AuCl3 and NaAuCl4 was similar but
[AuClACHTREUNG(PPh3)] was only effective when a silver salt (AgSbF6)
4
58
was added as co-catalyst. Owing to the low cost of NaAuCl4,
we selected this catalyst for further experiments oriented to
determine the scope of the reaction.
Next we tested the synthesis of unsymmetrical ethers with
a more difficult substrate, namely the secondary benzyl alco-
hol 1b (Table 2). To our delight, however, the etherification
of the two secondary alcohols 1b and 2 f (Table 2, entry 3)
was achieved in a very good yield (96%) when using the
[a] Isolated yield unless otherwise specified. [b] Unstable product; yield
determined by H NMR spectroscopy.
1
and secondary) with aliphatic primary and secondary alco-
hols.
gold
A
We subsequently tested the catalytic system in a more
challenging case, this being the preparation of ethers arising
from the reaction of an aliphatic tertiary alcohol with a pri-
mary alcohol (Table 4). The corresponding ethers were ob-
tained (Table 4, entries 1 and 2), but with modest and low
yields, respectively. Nevertheless, the examples we present
are the first to effectively carry out the etherification reac-
tion from such a mixture of alcohols with a transition-metal-
based catalytic system. To test the scope of the reaction fur-
ther, we attempted an etherification reaction arising from a
mixture of cyclooctanol (2i), an aliphatic secondary alcohol,
(2%) under mild conditions. Similar results were obtained
with primary (entries 1 and 2) and cyclic secondary alcohols
(entry 4).
The reaction could be extended to other secondary benzyl
alcohols (Table 3). Benzhydrol 1c (Table 3, entry 1), methyl
d,l-mandelate 1d (entry 2), sec-phenethyl alcohol 1e
(entry 3) and 9-fluorenol 1 f (entry 4) reacted with 2-propa-
nol 2 f to give the corresponding ethers with a moderate
yield. NaCl4Au, therefore, appears to be a suitable general
catalyst for the etherification of benzylic alcohols (primary
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Gold Catalysis
FULL PAPER
Table 4. GoldACHTREUNG(III)-catalysed etherification of tertiary alcohols.
(step A); 2) transfer of the hydroxyl group to the metal with
concomitant generation of the intermediate carbocation
(step B); and 3) trapping of the carbocation by the aliphatic
alcohol (step C). This catalytic cycle could account for the
results obtained.
À
Entry
1
R OH (2)
Catalyst[a]
A
Product (yield [%])[b]
3hj (23)
Conclusion
2
B
3gj (40)
We have described the first effective goldACHTRE(UGN III)-catalysed
method for the synthesis of unsymmetrical ethers from alco-
hols. The results show that primary and secondary benzylic
alcohols can be efficiently mixed with primary and secon-
dary aliphatic alcohols to provide the corresponding ethers
with moderate to good yields under mild conditions. The
catalyst is also active, although less effective, in the most
challenging case, that is, the etherification of an aliphatic
tertiary alcohol. Indeed, no precedents of this type are re-
ported for other transition-metal-based catalytic systems.
The use of a moderate excess of aliphatic alcohol allows the
unsymmetrical ether to be prepared with a good yield and
with no formation of the symmetrical ether derived from
either benzyl or tertiary alcohol. In addition, the water that
builds up in the reaction does not compete as a hydroxylic
reagent with the aliphatic alcohol, thus allowing a good con-
version without the use of dehydrating agents. As far as we
are aware, the reaction developed herein represents the first
example in which an alcohol acts as an electrophile in gold
chemistry. The intermediacy of a carbocation is consistent
not only with the profile of the reacting alcohols, but also
with the stereochemical outcome of the reaction when chiral
alcohols are used.
[a] Catalyst loading: 5% NaAuCl4 (A), 10% NaAuCl4 (B). [a] Isolated
yield.
3-phenylpropanol (2j) and a primary alcohol. Unfortunately,
the catalyst (5% NaAuCl4 loading) was ineffective in recov-
ering the initial unchanged materials even under forced con-
ditions. Therefore, the tertiary alcohol represents the bor-
derline point regarding the capacity of the catalyst to gener-
ate the electrophilic partner needed to accomplish the ether-
ification reaction. These findings might suggest that the re-
action occurs through a carbocation intermediate.[19]
We then analysed the stereochemical outcome of the reac-
tion to correlate this data with either the presence or ab-
sence of a carbocation in the reaction course. For this pur-
pose, we ran the reaction with homochiral (S)-1-indanol and
2-propanol. The formation of the corresponding racemic
ether, as proved by chiral HPLC, is in agreement with the
carbocation intermediacy (Scheme 2). Therefore, the forma-
tion of a benzyl or tertiary cation would be the crucial step
in the formation of the ether by alcohol dehydration.
Experimental Section
General remarks: Proton magnetic resonance and carbon magnetic reso-
nance were recorded at 300 and 75 MHz, respectively, with a Bruker AC-
300 spectrometer. Chemical shifts are reported in (d) ppm relative to the
TMS peak at d=0.0 ppm (1H spectra) and to the CDCl3 peak at d=
77.0 ppm (13C spectra). High Resolution Mass Spectra (HRMS) were de-
termined on a Fisons VG Autospec instrument. Reactions were moni-
tored by analytical thin-layer chromatography by using commercial alu-
minium sheets precoated (0.2 mm layer thickness) with silica gel 60 F254
(E. Merck), and visualisation was effected with short-wavelength UV
light (254 nm). Product purification by flash chromatography was per-
formed by using E. Merck silica gel (230–400 mesh).
Scheme 2. Etherification with racemisation of the chiral alcohol.
The simplified catalytic cycle shown in Scheme 3 contains
the following three steps: 1) coordination of the oxygen
atom of the benzyl alcohol (or tertiary alcohol) to the cata-
lytic species, which could be either NaAuCl4 or AuCl3
Materials: Commercial reagents were supplied by Aldrich and they were
used without further purification. Ethers 3ac,[20] 3ad,[16] 3ae,[18] 3af,[16]
3ag,[16] 3bd,[21] 3cf,[22] 3ef[20] and 3 ff[10] have been described previously.
Representative general procedure for the etherification reaction: Amix-
ture of alcohol 1 (0.4 mmol), alcohol 2 (2 mmol) and NaAuCl4 (2 mol%)
was added to a flask sealed with a Teflon screw-cap and was heated to
708C. After being refluxed for 1 h, the reaction mixture was cooled to
room temperature, diluted with ethyl acetate (5 mL), and filtered over
activated aluminium oxide. The solution was then evaporated under re-
duced pressure. The crude material was purified by flash column chroma-
tography (hexane).
1-[(Cyclopentylmethoxy)methyl]-4-methoxybenzene (3aa): Yield: 80%;
colourless oil; 1H NMR (CDCl3): d=7.19 (d, J=8.4 Hz), 6.78 (d, J=
Scheme 3. Catalytic cycle.
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G. Asensio et al.
8.4 Hz), 4.37 (s, 2H), 3.73 (s, 3H), 3.23 (d, J=7.1 Hz, 2H), 2.00 (sept.,
J=7.5 Hz, 1H), 1.61–1.70 (m, 2H), 1.41–1.42 (m, 4H), 1.12–1.21 ppm (m,
2H); 13C NMR (CDCl3): d=159.1, 131.0, 129.2, 113.8, 74.8, 72.6, 55.3,
39.5, 29.7, 25.5 ppm; HMRS (EI): m/z: calcd for C13H14O: 220.1463 [M]+;
found: 220.1469.
J=6.1 Hz, 1H), 3.61 (sept, J=6.0 Hz, 1H), 2.64–2.74 (m, 1H), 2.24–2.35
(m, 1H), 1.84–1.93 (m, 2H), 1.56–1.68 (m, 4H), 1.46–1.51 (m, 4H), 1.31–
1.38 ppm (m, 2H); 13C NMR (CDCl3): d=143.9, 143.2, 127.8, 126.3,
124.7, 124.6, 80.8, 78.9, 35.1, 34.2, 33.6, 29.9, 28.4, 28.2, 23.0, 22.8 ppm;
HMRS (EI): m/z: calcd for C16H22O: 230.1670 [M]+; found: 230.1668.
1-Methoxy-4-(neopentyloxymethyl)benzene (3ab): Yield: 58%; colour-
less oil; 1H NMR (CDCl3): d=7.18 (d, J=8.4 Hz), 6.78 (d, J=8.4 Hz),
4.38 (s, 2H), 3.73 (s, 3H), 3.01 (s, 2H), 0.84 ppm (s, 9H); 13C NMR
(CDCl3): d=158.8, 131.1, 128.8, 113.6, 80.5, 72.8, 55.2, 32.0, 26.7 ppm;
HMRS (EI): m/z: calcd for C13H20O: 208.1463 [M]+; found: 208.1463.
(Isopropoxymethylene)dibenzene (3cf): Yield: 56%; colourless oil;
1H NMR (CDCl3): d=7.15–7.32 (m, 10H), 5.43 (s, 1H), 3.62 (sept., J=
6 Hz, 1H); 1.16 ppm (d, J=6 Hz, 6H); 13C NMR (CDCl3): d=142.2,
128.2, 127.2, 127.0, 80.4, 69.0, 22.2 ppm; HMRS (EI): m/z: calcd for
C16H18O: 226.1357 [M]+; found: 226.1362.
(1-Isopropoxyethyl)benzene (3ef): Yield: 53%; colourless oil; 1H NMR
(CDCl3): d=7.20–7.30 (m, 8H), 4.50 (q, J=6 Hz, 1H), 3.44 (sept., J=
6 Hz, 1H), 1.37 (d, J=6 Hz, 3H), 1.11 (d, J=6 Hz, 3H), 1.06 ppm (d, J=
6 Hz, 3H); 13C NMR (CDCl3): d=144.8, 128.2, 127.1, 126.0, 74.5, 68.4,
24.7, 23.3, 21.3 ppm; HMRS (EI): calcd for C8H9O: 121.0653 [MÀ43]+;
found: 121.0640.
1-(Isopentyloxymethyl)-4-methoxybenzene (3ac): Yield: 60%; colourless
oil; H NMR (CDCl3): d=7.19 (d, J=8.4 Hz), 6.80 (d, J=8.4 Hz), 4.36 (s,
2H), 3.73 (s, 3H), 3.39 (t, J=6.7 Hz, 2H), 1.65 (sept., J=6.6 Hz, 1H),
1.42 (m, 2H), 0.82 ppm (d, J=6.6 Hz, 6H); 13C NMR (CDCl3): d=159.0,
130.7, 129.1, 113.7, 72.5, 68.5, 55.2, 38.5, 25.0, 22.6 ppm; HMRS (EI):
calcd for C13H20O: 208.1463 [M]+; found: 208.1463.
1
(9-Isopropoxy)fluorene (3 ff): Yield: 58%; colourless oil; 1H NMR
(CDCl3): d=7.53–7.59 (m, 4H), 7.18–7.33 (m, 4H), 5.50 (s, 1H), 3.74
(sept., J=6 Hz, 1H), 1.13 ppm (d, J=6 Hz, 6H); 13C NMR (CDCl3): d=
144.3, 140.4, 128.7, 127.4, 125.4, 119.8, 79.7, 69.9, 23.7 ppm; HMRS (EI):
m/z: calcd for C16H16O: 224.1201 [M]+; found: 224.1202.
1-(Ethoxymethyl)-4-methoxybenzene (3ad): Yield: 61%; colourless oil;
1H NMR (CDCl3): d=7.19 (d, J=8.4 Hz), 6.78 (d, J=8.4 Hz), 4.20 (q,
J=7.0 Hz, 2H), 3.71 (s, 3H), 1.15 ppm (t, J=7.0 Hz, 1H); 13C NMR
(CDCl3): d=158.7, 132.0, 128.7, 113.6, 72.7, 65.8, 55.6, 15.6 ppm; HMRS
(EI): calcd for C10H14O: 166.0993 [M]+; found: 166.0983.
[3-(tert-Pentyloxy)propyl]benzene (3hj): Yield: 23%; colourless oil;
1H NMR (CDCl3): d=7.07–7.22 (m, 5H), 3.25 (t, J=6.4 Hz, 2H), 2.61 (t,
J=7.8 Hz, 2H), 1.73–1.82 (m, 2H), 1.42 (q, J=7.5 Hz, 2H), 1.05 (s, 6H),
0.80 ppm (t, J=7.5 Hz, 3H); 13C NMR (CDCl3): d=142.3, 128.4, 128.2,
125.5, 74.4, 60.2, 32.7, 32.5, 32.1, 25.0, 8.2 ppm; HMRS (EI): m/z: calcd
for C14H22O: 205.1592 [M]+; found: 205.1548.
1-Methoxy-4-(pentyloxymethyl)benzene (3ae): Yield: 58%; colourless
oil; H NMR (CDCl3): d=7.18 (d, J=8.4 Hz), 6.79 (d, J=8.4 Hz), 4.35 (s,
2H), 3.72 (s, 3H), 3.36 (t, J=6.7 Hz, 2H), 1.50–1.55 (m, 2H), 1.23–1.28
(m, 4H), 0.79–0.84 ppm (m, 3H); 13C NMR (CDCl3): d=159.0, 130.7,
129.1, 113.6, 72.4, 70.1, 55.2, 29.4, 28.3, 22.5, 14.0 ppm; HMRS (EI): calcd
for C13H20O: 208.1463 [M]+; found: 208.1457.
1
1
(3-tert-Butoxypropyl)benzene (3gj): Yield: 40%; colourless oil; H NMR
1-(Isopropoxymethyl)-4-methoxybenzene (3af): Yield: 71%; colourless
oil; 1H NMR (CDCl3): d=7.19 (d, J=8.4 Hz), 6.79 (d, J=8.4 Hz), 4.3 (s,
2H), 3.71 (s, 3H), 3.58 (sept., J=6.1 Hz, 1H), 1.12 ppm (t, J=6.1 Hz,
6H); 13C NMR (CDCl3): d=158.9, 131.1, 129.0, 113.6, 70.5, 69.6, 55.2,
22.0 ppm; HMRS (EI): calcd for C11H16O: 180.1150 [M]+; found:
180.1146.
(CDCl3): d=7.09–7.24 (m, 4H), 3.30 (t, J=6.4 Hz, 2H), 2.63 (t, J=
8.1 Hz, 2H), 1.75–1.85 (m, 2H), 1.13 ppm (s, 9H); 13C NMR (CDCl3): d=
142.2, 128.4, 128.2, 125.6, 72.5, 60.7, 32.4, 32.1, 27.6 ppm; HMRS (EI):
calcd for C12H17O: 177.1279 [MÀ15]+; found: 177.1259.
1-(tert-Butoxymethyl)-4-methoxybenzene (3ag): Yield: 76%; colourless
1
oil; H NMR (CDCl3): d=7.18 (d, J=8.4 Hz), 6.79 (d, J=8.4 Hz), 4.30 (s,
2H), 3.71 (s, 3H), 1.21 ppm (s, 9H); 13C NMR (CDCl3): d=158.8, 131.9,
128.9, 113.7, 73.2, 63.7, 55.3, 27.7 ppm; HMRS (EI): calcd for C12H18O:
194.1306 [M]+; found: 194.1297.
Acknowledgements
Financial support by the Spanish Dirección General de Investigación,
Consolider Ingenio 2010 (CSD2007—00006) and the Generalitat Valenci-
ana 842/2005 and 027/2005) is gratefully acknowledged. We acknowledge
SCSIE (Universidad de Valencia) for access to instrumental facilities.
1-Methoxy-4-(tert-pentyloxymethyl)benzene (3ah): Yield: 58%; colour-
less oil; 1H NMR (CDCl3): d=7.19 (d, J=8.4 Hz), 6.78 (d, J=8.4 Hz),
4.20 (s, 2H), 3.71 (s, 3H), 1.52 (q, J=7.5 Hz, 1H), 1.15 (s, 6H), 0.85 ppm
(t, J=7.5 Hz, 3H); 13C NMR (CDCl3): d=158.7, 132.0, 128.7, 113.6, 75.2,
63.2, 55.2, 32.7; 25.2, 8.3 ppm; HMRS (EI): calcd for C13H20O: 208.1463
[M]+; found: 208.1461.
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1-(Cyclopentylmethoxy)-2,3-dihydro-1H-indene (3ba): Yield: 83%; col-
ourless oil; 1H NMR (CDCl3): d=7.11–7.32 (m, 4H), 4.18–4.85 (m, 1H),
3.26–3.37 (m, 2H), 2.29–3.03 (m, 1H), 2.62–2.76 (m, 1H), 2.21–2.32 (m,
1H), 2.05–2.15 (m, 1H), 1.91–2.02 (m, 1H), 1.62–1.72 (m, 2H), 1.44–1.51
(m, 4H), 1.16–1.21 ppm (m, 2H); 13C NMR (CDCl3): d=143.6, 143.1,
128.0, 126.2, 124.9, 124.7, 83.1, 73.2, 39.6, 32.3, 30.1, 29.6, 29.6, 25.3 ppm;
HMRS (EI): calcd for C15H20O: 216.1514 [M]+; found: 216.1515.
1-Ethoxy-2,3-dihydro-1H-indene (3bd): Yield: 47%; colourless oil;
1H NMR (CDCl3): d=7.31–7.33 (m, 2H), 7.10–7.18 (m, 2H), 4.48 (dd,
J=6.6, 4.3 Hz, 1H), 3.53 (q, J=7.0 Hz, 2H), 2.95–3.06 (m, 1H), 2.68–2.78
(m, 1H), 2.22–2.33 (m, 1H), 1.94–2.04 (m, 1H), 1.15 ppm (t, J=6.9 Hz,
3H); 13C NMR (CDCl3): d=143.8, 143.0, 128.1, 126.2, 124.9, 124.8, 82.9,
63.9, 32.4, 30.1, 15.5 ppm; HMRS (EI): m/z: calcd for C11H14O: 162.1044
[M]+; found: 162.1050.
1-Isopropoxy-2,3-dihydro-1H-indene (3bf): Yield: 96%; colourless oil;
1H NMR (CDCl3): d=7.27–7.30 (m, 1H), 7.10–7.17 (m, 3H), 4.91 (t, J=
6.2 Hz, 1H), 3.78 (sept., J=6.1 Hz, 1H), 2.92–3.02 (m, 1H), 2.71 (quint.,
J=7.7 Hz, 1H), 2.25–2.36 (m, 1H), 1.86–1.97 (m, 1H), 1.15 ppm (dd, J=
6.1, 1.0 Hz, (6H); 13C NMR (CDCl3): d=143.8, 143.3, 127.9, 126.3, 124.7,
124.6, 80.9, 70.2, 33.6, 29.9, 23.1, 22.5 ppm; HMRS (EI): calcd for
C12H16O: 176.1201 [M]+; found: 176.1204.
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1-(Cycloheptyloxy)-2,3-dihydro-1H-indene (3bi): Yield: 86%; colourless
oil; 1H NMR (CDCl3): d=7.26–7.29 (m, 1H), 7.11–7.16 (m, 3H), 4.90 (t,
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1522
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ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 1518 – 1523

Gold Catalysis
FULL PAPER
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ether (14% yield). On the other hand, indanol 1b and isopropanol
(2 f) gave a mixture of unsymmetrical ether (45%) and indene
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[18] The referees suggested that the HCl produced from the gold catalyst
could be responsible for the observed etherification reaction. To
assure that this possibility can be ruled out, several control experi-
ments were performed. In general, much less efficient transforma-
tions were achieved when reactions were catalysed by 5% HCl. For
instance, the reaction of 1a with 2 f gave a mixture of unsymmetrical
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Received: July 23, 2007
Published online: November 28, 2007
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