Solvent-free Br?nsted acid catalysed alkylation of arenes and heteroarenes with benzylic alcohols

Article abstract of DOI:10.1016/j.tet.2014.01.011

A simple and efficient alkylation of aromatic and heteroaromatic compounds via the direct S_N1-type nucleophilic substitution of benzylic alcohols in the presence of catalytic amounts of the strong Br?nsted acid o-benzenedisulfonimide under neat conditions is herein reported. A library of di- and triaryl (and heteroaryl) methanes was prepared in good yields and high regioselectivity. The observed reactivity was shown to be in agreement with Mayr's nucleophilicity and electrophilicity scales.

Full text of DOI:10.1016/j.tet.2014.01.011

Tetrahedron 70 (2014) 1818e1826
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Solvent-free Brønsted acid catalysed alkylation of arenes and
heteroarenes with benzylic alcohols
*
Margherita Barbero , Silvano Cadamuro, Stefano Dughera, Marta Rucci, Giulia Spano,
Paolo Venturello
ꢀ
Dipartimento di Chimica, Universita di Torino, Via P. Giuria 7, 10125 Torino, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple and efficient alkylation of aromatic and heteroaromatic compounds via the direct SN1-type
nucleophilic substitution of benzylic alcohols in the presence of catalytic amounts of the strong
Brønsted acid o-benzenedisulfonimide under neat conditions is herein reported. A library of di- and
triaryl (and heteroaryl) methanes was prepared in good yields and high regioselectivity. The observed
reactivity was shown to be in agreement with Mayr’s nucleophilicity and electrophilicity scales.
Ó 2014 Elsevier Ltd. All rights reserved.
Received 25 September 2013
Received in revised form 23 December 2013
Accepted 6 January 2014
Available online 10 January 2014
Keywords:
SN1-type reactions
Benzylic alcohols
Triarylmethanes
Nucleophilicity
Brønsted acid catalyst
1. Introduction
biologically active substances, as well as in various classes of
functional materials. Comprehensive reviews of direct nucleophilic
The nucleophilic substitution of inexpensive and abundantly
available alcohols is a useful way to access a variety of compounds
via direct dehydrative coupling,1 although alcohol pre-activation is
often required. This can be achieved by transforming the poor hy-
droxide leaving group into more reactive derivatives, such as ha-
lides, tosylates, mesylates and other esters (whose use however is
less environmentally friendly and less convenient in terms of atom
economy), or by using excess amounts of a Brønsted acid or stoi-
chiometric amounts of a Lewis acid. However, the use of the so-
SN-1 type alcohol reactions and of stereoselective organocatalytic
alkylations via carbenium ions were published by Cozzi in 2011 and
2013,3 whilst FriedeleCrafts benzylation reactions using alcohols
were reviewed by Bandini2 and Rueping4 in 2009 and 2010,
respectively.
When investigating the literature for reactions between
benzylic and benzhydrylic alcohols and C-nucleophiles, many
acid-catalysed reactions were found in both organic solvents and
water. Catalytic activation has been accomplished in the presence
of Lewis acids, such as Fe(ClO4)3$xH2O,5 NbCl5,6 FeCl3,7 InBr3,8
InCl3,9 and lanthanoid triflates.10 Some lanthanoid triflates have
been successfully employed as the catalysts in ionic liquid sol-
vents,11 whereas Fe(III)- or Zn(II)-based ionic liquids have been
reported to catalyse the direct nucleophilic substitution reactions
of alcohols in the regioselective benzylation of arenes and het-
eroarenes and other C-nucleophiles.12 Common Brønsted acid
catalysts have also been used, such as TfOH and p-TsOH in neat
conditions,13 p-TsOH and solid-supported sulfonic acids,14
NaHSO4/SiO2,15 TfOH in MeCN or in ionic liquids,11 silica-
supported phosphomolybdic acid,16 and montmorillonite.17 Wa-
ter was the solvent for the DBSA catalyst,18 however reactions
carried out ‘on water’,19 in high temperature water20 and in the
special medium of a gluconic acid aqueous solution21 have also
been reported. Finally, organocatalytic conditions can be found in
the use of C6F5B(OH)2 acid.22
called
p-activated alcohols, in the presence of Brønsted or Lewis
acids in catalytic amounts, has recently been suggested as an effi-
cient source of carbocation electrophiles.2 The direct catalytic SN1-
type alcohol reaction is a very green process since it produces water
as the only by-product and, when arenes and heteroarenes are the
nucleophilic partners, is an environmental benign FriedeleCrafts
reaction, as no extra activation or protection/deprotection steps are
required.
When primary or secondary benzylic alcohols are used, the re-
action products are di- and triarylmethanes (and heteroaryl ana-
logues), which are important substructures in
a variety of
* Corresponding author. Tel.: þ39 011 6707645; fax: þ39 011 6707642; e-mail
address: margherita.barbero@unito.it (M. Barbero).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.01.011

M. Barbero et al. / Tetrahedron 70 (2014) 1818e1826
1819
In continuation of our interests in acid catalysed CeC bond
forming reactions under solvent-free conditions, and in order to
plan a more detailed study into the synthetic usefulness of a class of
stable isolated diarylcarbenium salts recently reported by us,23 we
decided to undertake a comparative study of direct alcohol nucle-
ophilic substitution using primary and secondary benzylic alcohols
in the presence of the strong Brønsted acid o-benzenedisulfoni-
mide (1)24 (Fig. 1).
All tested reagents (alcohols 2aej, nucleophiles 3aeh and sty-
renes 15a, b) and the corresponding isolated or attempted Frie-
deleCrafts alkylation products 4e14 are reported in Table 1, whilst
the list of purified and characterised products is reported in Table 2.
The results of the successful (reported in Table 3) and un-
successful reactions were reasonably rationalised using electro-
philicity and nucleophilicity parameters determined by H. Mayr
et al.25
The first alcohol investigated was bis(4-methoxyphenyl)meth-
anol (2a). The reaction conditions were very mild when 2a was
reacted with electron-rich aromatic and heteroaromatic substrates
3aee in a molar ratio of 2:3¼1:2 (the nucleophile excess reported
in most literature papers).
Room temperature and very short reaction times gave the cor-
responding triarylmethanes 4aee as the only products in high
yields and purity (Table 3, entries 1e7). Under these conditions, the
competitive formation of the symmetric ether via acid-catalysed
dehydration of 2a was never observed, and the water formed as
the only by-product did not influence the course of the reaction.
The reactivity is so high that dialkylation products were isolated in
significant amounts in the reactions with aromatics 3b and 3d;
their formation, however, could be limited by carrying out the re-
action in the presence of a greater nucleophile excess (molar ratio
2:3¼1:10) (Table 3, compare entries 2 and 5 with entries 3 and 6).
In order to evaluate the validity and range of the methodology,
some reactions between benzhydryl alcohols 2bed and arenes 3a,
3d and 3e were carried out (Table 3, entries 8e15). Triarylmethanes
5e7 were generally obtained in good yields using a variable excess
of the nucleophile (molar ratio 2:3¼1:1.2 or 1:2), although with
slightly longer times or under heating. When using alcohol 2c, trace
amounts of symmetric bis(diphenylmethyl) ether were detected in
the reaction mixture. The reactivity was only slightly affected by
the halogen inductive effect; the reactions of 2d gave products 7a
and 7b in surprisingly high yields upon heating.
Fig. 1. o-Benzenedisulfonimide.
In this paper, we report successful (and unsuccessful) results
obtained in the FriedeleCrafts alkylation of activated arenes and
heteroarenes and explain such results on the basis of the most
comprehensive nucleophilicity and electrophilicity scales tabulated
by Professor Herbert Mayr.25
2. Results and discussion
The direct catalytic SN1-type alcohol nucleophilic sub-
stitution proceeds via an intermediate carbenium species,
whose stability (and reactivity) is strongly influenced by the
electronic effects of the aryl (or alkyl) substituents. In light of
this, we decided to study the reaction using various diary-
lmethanols and activated nucleophiles in neat conditions and in
the presence of a catalytic amount of the acid 1 (10 mol %). The
catalyst amount was maintained constant, although it is likely
that some reactions may be carried out in the presence of
smaller quantities. Then, the reaction conditions were applied
to primary and secondary benzylic alcohols and, finally, some
explorative reactions were run by using styrenes as the elec-
trophiles. Starting from alcohols, a competitive dehydration
reaction was sometimes observed, although the same acidic
conditions were able to catalyse ether cleavage without reagent
loss (Scheme 1).
The lack of reactivity when using alcohols 2b is quite in-
teresting: the expected product 5b was obtained from the reaction
with the indole (3e) in good yields (Table 3, entry 9), whilst the
reaction with 3a did not proceed even in harsh conditions. The
reason for such behaviour can be found in the low electrophilicity
of the highly stabilized carbenium ion coupled with the lower
nucleophilic properties of the latter aromatic compound. This was
confirmed by the reactions of 2b with 3d and 3h; with pyrrole,
Scheme 1. Arene and heteroarene FriedeleCrafts alkylation of alcohols and styrenes.

1820
M. Barbero et al. / Tetrahedron 70 (2014) 1818e1826
Table 1
Reagents and products
Alcohols 2 and styrenes 15
Nucleophiles 3
Products 4e14
2a
3a
4
2b
3b
5
2c
3c
6
7
2d
3d
2e
2f
3e
3f
8
9
2g
2h
3g
3h
10
11
2i
2j
12
13
15a
15b
14
Table 2
Isolated and characterised products
4a
4b
4c
4d
5b
4e
5c
5a
6a

M. Barbero et al. / Tetrahedron 70 (2014) 1818e1826
1821
Table 2 (continued)
6b
7a
7b
8a
9a
8b
9b
8c
9c
13a
14c
14a
16
14b
17
heating was required and the yield of 5a was modest, whereas the
more nucleophilic 3h gave product 5c in very high yield (Table 3,
entries 8 and 10).
These results can be understood by referring to the extensive
works of Herbert Mayr and co-workers, which represent
a milestone in the study of carbon-carbon forming reactions via
direct electrophileenucleophile coupling.25 Many SN1-type re-
actions can be rationally designed by means of one solvent-
independent electrophilicity parameter (E) and two solvent-
dependent nucleophilicity ones (the nucleophilicity parameter N
Table 3
o-Benzenedisulfonimide (1) catalysed alkylation of arenes and heteroarenes by primary and secondary benzylic alcoholsa
Entry
2
3
Molar ratio 2:3
T (ꢀC)
Time (min)
Products
Product yields (%)b
Literature product yieldsc
995
1
2
3
4
5
6
7
8
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
2c
3a
3b
3b
3c
3d
3d
3e
3d
3e
3h
3a
3e
3a
3e
3a
3d
3d
3e
3a
3c
3c
3e
3a
3f
1:2
1:2
1:10
1:2
1:2
rt
rt
rt
rt
rt
rt
rt
70
rt
15
15
15
15
15
10
15
5 h
5
5.5 h
90
120
45
6 h
5.5 h
120
90
4a
100
64 (31)d
86 (10)d
87
4b
4b
4c
4d
4d
4e
5a
5b
5c
6a
6b
7a
7b
8a
8b
8b
8c
905
9418
52 (39)d
86 (14)d
94
1:10
1:2
1:10
1:1.2
1:2
1:1.2
1:1.2
1:1.2
1:1.2
1:2
1:10
1:10
1:1.2
1:2
91,18 925
48
96
98
83
81
95
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
30
rt
2c
60
60
60
60
70
40
rt
8518
955
2d
2d
2e
2e
2e
2e
2f
2f
2f
2f
2j
82
50e
23 (42)d
53 (27)d
94
21 (26)33
8035
60
60
rt
120
4.5 h
30
3 h
5 h
7 h
7 h
2 h
30
9a
87f
1:2
1:10
1:2
9b
9b
9c
13a
14b
14c
13a
14a
35f
60
60
90
60
60
130
60
65
48f
1:2
82
66
50
66
15b
15b
15a
15b
1:1.2
1:1.2
1:1.2
1:1.2
6613
3g
3a
3a
67
a
Reaction conditions: o-benzenedisulfonimide (1) 10 mol %, neat conditions.
Yields refer to pure isolated products.
Product yield reported in the literature using benzylic alcohols as alkylating reagents.
Isolated dialkylation product yield is reported in parentheses.
b
c
d
e
Benzaldehyde, bis(4-dimethylaminophenyl)phenylmethane (16) and bis[(4-dimethylaminophenyl)phenylmethyl] ether (17) were identified as by-products (see
Experimental section).
f
Traces of symmetric ethers were detected by GC and GCeMS analyses.

1822
M. Barbero et al. / Tetrahedron 70 (2014) 1818e1826
and the sensitivity parameter s).26 In this scale, the carbocation that
derives from alcohol 2a represents the reference compound (E¼0),
more reactive benzhydrylium cations are placed at the top of the
list (E>0), whilst less reactive cations are placed at the bottom
(E<0). In fact, Mayr introduced a predictive ‘rule of thumb’ in order
to predict the feasibility of a certain reaction between an electro-
phile and a nucleophile. Although steric effects are neglected in
these studies and our reactions are carried out in solvent-free
conditions (i.e., in high concentrations, which is not a negligible
nucleophilic sites: the hydroxyl group and the ring C-1, whose
nucleophilic character is presumably increased by the para-dime-
thylamino group. The carbenium ion can then undergo a reductive
nucleophilic attack by 2e, which simultaneously results in the re-
lease of benzaldehyde.
consideration),
the
results obtained
in
the
electro-
phileenucleophile combinations here reported can be reasonably
explained with reference to the corresponding E and N values,
when determined by Mayr, or by an extrapolation of similar ref-
erence compound N values. The most reactive carbenium ions used,
like those generated from alcohols 2a, 2c and 2d, reacted with
arenes and heteroarenes of varying nucleophilicity under mild
conditions in good overall conversions. The least reactive, namely
the carbenium ion derived from alcohol 2b, is only able to react
with high N value aromatics.
In order to confirm these data, we decided to test alcohol 2e in
the coupling reactions with 3a, 3d and 3e. Although not tabulated,
the electrophilicity of the corresponding carbenium ion should be
found between that of 2b and 2c. Whilst similar results were ob-
tained in the reaction with 3e (highest N value) (entries 9 and 18),
the reaction of 2e with nucleophile 3d (lower N value) gave better
conversion than alcohol 2b in terms of reaction time and yields
(entries 8 and 16e17). As observed in the reaction between 2a and
3d, a dialkylation product was isolated, when higher concentration
(entry 5) or higher temperature (entry 16) were used. The mono-
alkylation product (N value higher than the unsubstituted pyrrole)
undergoes FriedeleCrafts alkylation in a competitive reaction.
However, the most significant result would have been observed in
the reaction of 2e with 3a (lowest expected N value). Quite un-
expectedly, product 8a was obtained in a modest yield (Table 3,
entry 15), and formation of the symmetric ether 17 by acid de-
hydration of 2e was observed, along with traces of benzaldehyde
(GC and GCeMS analyses) and a non-negligible amount of the by-
product 16. As in the general pathway depicted in Scheme 2, al-
cohol 2e protonation by the protic acid 1 gives rise to the in-
termediate carbenium ion A, which can undergo nucleophilic
alkylation by nucleophile 3a (or free alcohol 2e) to afford the ex-
pected product 8a or the corresponding symmetric ether 17. The
ether can then undergo acid cleavage (as in Scheme 1) and there-
fore give rise to the formation of alcohol 2e and the reactive car-
benium ion A.
Scheme 3. Proposed mechanism for the formation of 16.
Similar behaviour has been reported during the attempted re-
duction of 4,40-bis(dimethylamino)benzhydrol, where the observed
mixture of 4-dimethylaminobenzaldehyde and dimethylaniline
was ascribed to alcohol acidic cleavage.27 The formation of 16 and
17 was confirmed by reacting 2e in the presence of 5 mol % of acid 1
in toluene; details are reported in the Experimental section. In our
opinion, this reaction deserves more attention, so further studies
are currently underway.
Then primary benzylic alcohols 2fei were reacted with some
representative aromatic substrates. Heating was necessary in order
to complete the reaction, whilst molar ratio (generally 2:3¼1:2),
neat conditions and catalyst amount (1, 10 mol %) were kept un-
altered. The substituent effect on the intermediate primary carbo-
cation formation and reactivity was evident. Whilst alcohol 2f gave
expected diarylmethanes 9a, 9b and 9c under mild reaction con-
ditions (Table 3, entries 19e22), reactions of 2h with 3a and 3e only
Scheme 2. Acid-catalysed competitive reactions of alcohol 2e.
The formation of triarylmethane 16 can probably occur through
the reaction mechanism of Scheme 3. Under our reaction condi-
tions, an unprecedented redox reaction between the intermediate
carbenium ion A and 2e was observed. Alcohol 2e bears two
afforded traces of the benzylation products; furthermore, alcohols
2g and 2i did not react with 3a at all. Some reactions were also run
in a solvent (toluene or THF at reflux), but unsuccessfully. In the
course of some of the above reactions, the formation of ethers from

M. Barbero et al. / Tetrahedron 70 (2014) 1818e1826
1823
the starting alcohols and their conversions into the final products
were observed. Both dehydration and ether cleavage reactions are
acid-catalysed equilibria, although the reaction with aromatics 3
proved that they are stronger nucleophiles than alcohols 2.
Finally, we decided to explore the reaction of the secondary
benzylic alcohol 2j, which presents one aryl and one alkyl moiety,
with some of the above nucleophiles. From the reaction with 3a, the
1,1-diarylalkane 13a was obtained in a good yield (Table 3, entry
23). GC analyses of the reaction mixture initially showed the for-
mation of two diastereomeric ethers (which derive from de-
hydration of the commercial racemic 2j) and then their conversion
to the desired product 13a.
triaryl (or heteroaryl) methanes and diarylmethanes. Primary and
secondary benzylic alcohols were used as the carbenium ion source
in the presence of catalytic amounts of the protic acid o-benzene-
disulfonimide, whose well-known recoverability and recycla-
bility24b represents
a further advantageous aspect of the
methodology. In most cases, successful and unsuccessful results
were shown to be in agreement with Mayr’s nucleophilicity and
electrophilicity scales. Furthermore, some explorative 100% atom
economy reactions were carried out using styrenes as the alkylating
agents in the synthesis of 1,1-diarylethanes. The advantages and
disadvantages of the synthetic procedure are discussed, along with
an explanation of unwanted observed side-reactions.
When 2j was reacted with pyrrole (3d) or indole derivatives
3eef, quite surprisingly, only starting reagents were detected along
with acid-catalysed polymerization products in the reaction mix-
ture, even under heating for long times. In particular, in the reaction
of 2j with 3f, the indole trimer 18 was isolated and fully charac-
terised. Although the formation of this product via acid-catalysed
polymerization is well documented in literature,28 we were able
to confirm this by heating indole in the presence of 10 mol % of o-
benzenedisulfonimide (1) at 60 ꢀC in neat conditions. Stopping the
reaction after 5 h, compound 18 was isolated, still in the presence of
indole, in 61% yield (Fig. 2).
4. Experimental section
4.1. General experimental
All the reactions were run in vials using analytical grade re-
agents, and were monitored by TLC, GC, GCeMS and NMR spec-
trometry. GCeMS spectra were recorded with an AT5973N mass
selective detector connected to an AT6890N GC cross-linked methyl
silicone capillary column. 1H NMR and 13C NMR spectra were
recorded in CDCl3 with a Bruker Avance 200 spectrometer at
200 MHz and 50 MHz, respectively; chemical shifts are given in
parts per million relative to CDCl3. IR spectra were recorded on an
IR PerkinElmer UATR Two. ESI-MS spectra were obtained using
a Waters micromass ZQ spectrometer equipped with an ESI ion
source. TLC were performed on Fluka silica gel TLCPET foils GF 254,
ꢁ
2e25
m
m, layer thickness 0.2 mm, medium pore diameter 60 A.
Plates were visualized using UV light (254 nm). Column chroma-
ꢁ
tography was carried out on SiO2 (pore size 70 A, 70e230 mesh).
Fig. 2. Indole trimer.
Petroleum ether refers to the fraction boiling in the range 40e60 ꢀC
and is abbreviated as PE. Commercially available reagents and
solvents were purchased from Aldrich and were used without pu-
rification or distillation prior to use. Alcohols 2b and 2e were pre-
pared via reduction of the corresponding ketones with NaBH4 in
methanol as described in literature.29 o-Benzenedisulfonimide (1)
was prepared as described in literature.24 Details for the reactions
and yields for the pure (GC, GCeMS, TLC, 1H and 13C NMR) isolated
products are listed in Table 3. Structure and purity of known
products were confirmed by comparison of their physical and
spectral data (IR, MS, 1H NMR and 13C NMR) with those reported in
literature.
Accordingly, in the reaction of 2j with 2-methylindole (3g),
where acid polymerization is prevented by the substitution in the
2-position, the expected alkylation product was observed by
GCeMS analysis and 1H NMR spectroscopy, although as a mixture
with presumable dialkylation products.
The impossibility of obtaining pure alkylation products 13 under
our reaction conditions may be explained by the lower reactivity of
the alcohol 2j (confirmed by long reaction times and heating) when
compared with the competitive indole polymerization and/or by
the lower indole nucleophilicity with respect to 1,2,4-trimetho
xybenzene.
With the aim of preparing compounds 13, we thought that
styrenes 15 could act as electrophiles in the presence of the acid
catalyst 1 (Scheme 1), in a reaction, which presents 100% atom
economy. The reactions were run in neat conditions, under heating
and in the presence of 10 mol % of 1. Trimer 18 was obtained from
styrene (15a) and 3f, while only traces of the expected product
were detected by GCeMS analyses. Gratifyingly, compounds 14b
and 14c were, on the contrary, obtained from 4-methoxystyrene
(15b) and indoles 3f and 3g, although in modest yields (Table 3,
entries 24e25). These results prompted us to test the reaction of
15a and 15b with 1,2,4-trimethoxybenzene (3a); expected products
13a and 14a were obtained in rather good yields (Table 3, entries
26e27).
4.2. General procedure for di- and triaryl (and heteroaryl)
methane 4e14 syntheses
A mixture of alcohol 2 (1.0 mmol) or styrene 15, aromatic
compound 3 (mmol as in Table 3) and o-benzenedisulfonimide (1,
10 mol %, 0.022 g) was stirred at rt (or under heating, as reported in
Table 3) in a vial until TLC, GC and GCeMS analyses shown the
almost complete conversion of 2 (or 15). The reaction mixture was
then treated with CH2Cl2/H2O (1:1, 20 mL). The aqueous phase was
extracted with CH2Cl2 (2ꢁ20 mL). The combined organic extracts
were dried with Na2SO4 and concentrated under reduced pressure.
The crude residue was purified by column chromatography (silica
gel, PE/AcOEt or PE/Acetone or PE/EE).
A direct comparison of our results with Mayr’s database, in these
cases, is less easy due to the lack of reported electrophilicity values
for the primary or secondary carbenium ions taken in consider-
ation. Furthermore, competitive dehydration or acid-catalysed
polymerisation reactions prevail in these reagent combinations.
4.2.1. Bis(4-methoxyphenyl)(2,4,5-trimethoxyphenyl)methane
(4a).5 Chromatographic eluent: PE/AcOEt¼7:3; white solid (0.39 g,
quantitative yield); mp 124e125 ꢀC (CH2Cl2/PE) [lit. 127 ꢀC]; IR
n
(cmꢂ1): 3030, 2955, 2839, 1606, 1507, 1242, 1203, 1175, 1029, 762;
3. Conclusion
1H NMR (200 MHz, CDCl3):
d
¼3.59 (s, 3H), 3.62 (s, 3H), 3.72 (s, 6H),
3.82 (s, 3H), 5.71 (s, 1H), 6.39 (s, 1H), 6.48 (s, 1H), 6.75 (d, J¼8.8 Hz,
In conclusion, we have reported a new, efficient, benign,
solvent-free FriedeleCrafts alkylation method for the synthesis of
4H), 6.95 (d, J¼8.8 Hz, 4H); 13C NMR (50 MHz, CDCl3):
¼47.3, 55.0
d
(2C), 55.9, 56.5, 56.7, 97.9, 113.3 (4C), 114.4, 124.9 (q), 130.0 (4C),

1824
M. Barbero et al. / Tetrahedron 70 (2014) 1818e1826
136.4 (q, 2C), 142.6 (q), 147.9 (q), 151.2 (q), 157.6 (q, 2C); MS (EI): m/z
yield); IR
780, 712; 1H NMR (200 MHz, CDCl3):
n
(cmꢂ1): 3397, 3241, 2880, 2793, 1607, 1514, 1335, 1163,
(%) 394 [Mþ](100), 379 (18), 363 (40), 121 (25).
d
¼2.92 (s, 12H), 5.28 (s, 1H),
5.80e5.86 (m, 1H), 6.12e6.18 (m, 1H), 6.60e6.65 (m, 1H), 6.68 (d,
J¼8.8 Hz, 4H), 7.06 (d, J¼8.8 Hz, 4H), 7.82 (br s, 1H); 13C NMR
4.2.2. Bis(4-methoxyphenyl)(2,4-dimethoxyphenylphenyl)methane
(4b).5 Chromatographic eluent: PE/AcOEt¼8:2; white solid (0.31 g,
(50 MHz, CDCl3):
d
¼40.7 (4C), 48.6, 107.1, 107.9, 112.6 (4C), 116.5,
86% yield); mp 85e86 ꢀC (CH2Cl2/PE) [lit. 94e95]; IR
n
(cmꢂ1):
129.3 (4C), 131.9 (q, 2C), 135.1 (q), 149.1 (2C); MS (EI): m/z (%) 319
(Mþ,100), 199 (55); calcd for C21H25N3: C 78.96%; H 7.89%; N 13.15%,
found: C 78.90%; H 7.81%; N 13.10%.
3030, 2954, 2833, 1605, 1586, 1497, 1241, 1207, 1173, 1033, 805; 1H
NMR (200 MHz, CDCl3):
¼3.66 (s, 3H), 3.74 (s, 9H), 5.70 (s, 1H),
d
6.32e6.45 (m, 2H), 6.71 (d, J¼9.4 Hz, 1H), 6.76 (d, J¼9.6 Hz, 4H),
6.96 (d, J¼9.6 Hz, 4H); 13C NMR (50 MHz, CDCl3):
d
¼47.2, 55.0 (2C),
4.2.7. Bis(4-dimethylaminophenyl)(1-methyl-3-indolyl)methane
(5b).31 Chromatographic eluent: PE/AcOEt¼7:3; white solid
(0.37 g, 96% yield); mp 182.9e183.9 ꢀC (CH2Cl2/PE) [lit.173e174 ꢀC];
55.1, 55.4, 98.5, 103.5, 113.2 (4C), 125.7 (q), 130.0 (4C), 130.4, 136.5
(q, 2C), 157.5 (q, 2C), 157.7 (q), 159.1 (q); MS (EI): m/z (%) 364
[Mþ](100), 349 (20), 333 (55), 257 (40), 121 (30).
IR
NMR (200 MHz, CDCl3):
n
(cmꢂ1): 3030, 2873, 2805, 1606, 1514, 1325, 1239, 804, 749; 1H
As reported in the results and discussion section, 1,5-bis[bis(4-
methoxyphenyl)methyl]-2,4-dimethoxybenzene was isolated as
d¼2.87 (s, 12H), 3.64 (s, 3H), 5.47 (s, 1H),
6.41 (s, 1H), 6.64 (d, J¼8.6 Hz, 4H), 6.88e6.98 (m, 1H), 7.07 (d,
a
dialkylation product; white solid (0.03 g, 10% yield); mp
158.5e159.5 ꢀC (CH2Cl2/PE); IR (cmꢂ1): 3030, 2920, 2834, 1606,
1583, 1507, 1242, 1175, 1032, 817; 1H NMR (200 MHz, CDCl3):
J¼8.8 Hz, 4H), 7.14e7.26 (m, 3H); 13C NMR (50 MHz, CDCl3):
¼32.4,
d
n
40.7, 46.6, 108.8, 112.5 (4C), 118.4, 119.5 (q), 120.1, 121.2, 127.4 (q),
128.4, 129.3 (4C), 133.1 (2C, q), 137.3 (q), 148.7 (2C, q).
d
¼3.66 (s, 6H), 3.71 (s, 12H), 5.58 (s, 2H), 6.25 (s, 1H), 6.38 (s, 1H),
6.65 (d, J¼8.8 Hz, 8H), 6.80 (d, J¼8.8 Hz, 8H); 13C NMR (50 MHz,
4.2.8. Bis(4-dimethylaminophenyl)(3-guaiazulenyl)methane
CDCl3):
d
¼47.3 (2C), 54.9 (4C), 55.7 (2C), 95.3, 113.1 (8C), 124.3 (q,
(5c). Chromatographic eluent: PE/EE¼8:2; blue solid (0.43 g, 95%
2C), 129.8 (8C), 132.2, 136.5 (q, 4C), 156.0 (q, 2C), 157.4 (q, 4C); calcd
for C38H38O6: C 77.26%; H 6.48%, found: C 77.20%; H 6.42%.
yield); mp 98e99 ꢀC (CH2Cl2/PE); IR (cmꢂ1): 2948, 2810, 1613,
n
1516, 1444, 1347, 1167, 796; 1H NMR (200 MHz, CDCl3):
d
¼1.33 (d,
J¼7.0 Hz, 6H), 2.54 (s, 3H), 2.90 (s, 12H), 2.91 (s, 3H), 2.99
(septuplet, J¼7.0 Hz, 1H), 6.34 (s, 1H), 6.65 (d, J¼8.8 Hz, 4H), 6.75
(d, J¼11.0 Hz, 1H), 6.92 (d, J¼8.8 Hz, 4H), 7.19 (s, 1H), 7.20 (dd,
J¼10.6 and 2.0 Hz, 1H), 8.06 (d, J¼2.0 Hz, 1H); 13C NMR (50 MHz,
4.2.3. Bis(4-methoxyphenyl)(5-methyl-2-furyl)methane
(4c).18,30 Chromatographic eluent: PE/AcOEt¼8:2; solid (0.27 g,
87% yield); mp 71e72 ꢀC (CH2Cl2/PE); IR
n
(cmꢂ1): 3030, 2950,
2845, 1615, 1506, 1240, 1207, 1174, 1029, 786; 1H NMR (200 MHz,
CDCl3):
d
¼13.0, 24.5 (2C), 27.2, 37.5, 40.7 (4C), 49.8, 112.4 (4C),
CDCl3):
d
¼2.22 (s, 3H), 3.75 (s, 6H), 5.27 (s, 1H), 5.68e5.71 (m, 1H),
123.7 (q), 126.4, 130.1 (4C), 131.2 (q), 132.3 (q), 133.2, 134.3, 135.3
(q, 2C), 137.6 (q), 138.6 (q), 140.7, 145.3 (q), 148.5 (q, 2C); calcd for
5.82e5.88 (m, 1H), 6.81 (d, J¼8.8 Hz, 4H), 7.06 (d, J¼8.8 Hz, 4H); 13
C
NMR (50 MHz, CDCl3):
d¼13.5, 49.2, 55.0 (2C), 105.8, 108.6, 113.6
C32H38N2: C 85.28%; H 8.50%; N 6.22%, found: C 85.23%; H 8.55%; N
6.30%.
(4C), 129.5 (4C), 134.5 (q, 2C), 151.2 (q), 155.5 (q), 158.1 (q, 2C); MS
(EI): m/z (%) 308 [Mþ](100), 265 (95), 210 (75).
4 . 2 . 9 . D i p h e n y l ( 2 , 4 , 5 - t r i m e t h o x y p h e n y l ) m e t h a n e
4 . 2 . 4 . B i s ( 4 - m e t h o x y p h e n y l ) ( 2 - p y r r o l y l ) m e t h a n e
(6a).5,32 Chromatographic eluent: PE/EE¼7:3; white solid (0.33 g,
(4d). Chromatographic eluent: PE/AcOEt¼8:2; light yellow oil
quantitative yield); mp 116e117 ꢀC (CH2Cl2/PE) [lit. 125 ꢀC]; IR
n
(0.25 g, 86% yield); IR
n
(cmꢂ1): 3374, 2950, 2839, 1690, 1605, 1507,
(cmꢂ1): 3030, 2954, 2822, 1601, 1509, 1437, 1204, 1028, 702; 1H
NMR (200 MHz, CDCl3):
¼3.59 (s, 3H), 3.62 (s, 3H), 3.84 (s, 3H),
5.84 (s, 1H), 6.40 (s, 1H), 6.50 (s, 1H), 7.00e7.10 (m, 4H), 7.13e7.28
(m, 6H); 13C NMR (50 MHz, CDCl3):
1241, 1173, 1028, 813, 717; 1H NMR (200 MHz, CDCl3):
d¼3.74 (s,
d
6H), 5.32 (s, 1H), 5.73e5.78 (m, 1H), 6.08e6.14 (m, 1H), 6.62e6.68
(m, 1H), 6.80 (d, J¼8.4 Hz, 4H), 7.06 (d, J¼8.8 Hz, 4H), 7.76 (br s, 1H);
d
¼49.0, 55.9, 56.4, 56.6, 98.0,
13C NMR (50 MHz, CDCl3):
d¼48.8, 55.1 (2C), 107.5, 108.0, 113.7 (4C),
114.7, 124.2 (q), 125.9 (2C), 127.9 (4C), 129.2 (4C), 142.7 (q), 143.9 (q,
2C), 148.0 (q), 151.3 (q); MS (EI): m/z (%) 334 [Mþ](100), 319 (20),
303 (25).
116.8, 129.6 (4C), 134.2 (q), 135.5 (q, 2C), 158.1 (q, 2C); MS (EI): m/z
(%) 293 (Mþ, 100%), 262 (25), 186 (95); calcd for C19H19NO2: C
77.79%; H 6.53%; N 4.77%, found: C 77.70%; H 6.48%; N 4.70%.
As reported in the results and discussion section, 2,5-bis[bis(4-
methoxyphenyl)methyl]pyrrole was isolated as a dialkylation prod-
uct; white solid (0.04 g, 14% yield); mp 148.0e149.0 ꢀC (CH2Cl2/PE);
4 . 2 . 1 0 . D i p h e n y l ( 1 - m e t h y l - 3 - i n d o l y l ) m e t h a n e
(6b).32 Chromatographic eluent: CH2Cl2; solid (0.24 g, 81% yield);
mp 134.5e136 ꢀC (CH2Cl2/PE); IR
n
(cmꢂ1): 3023, 2857, 1448, 1227,
IR
n
(cmꢂ1): 3333, 2845, 1606, 1506, 1247, 1173, 1030, 801; 1H NMR
739, 700; 1H NMR (200 MHz, CDCl3):
6.41 (s, 1H), 6.82e7.03 (m, 1H), 7.10e7.30 (m, 13H); 13C NMR
(50 MHz, CDCl3):
d
¼3.67 (s, 3H), 5.67 (s, 1H),
(200 MHz, CDCl3):
d
¼3.72 (s,12H), 5.20 (s, 2H), 5.52 (d, J¼2.6 Hz, 2H),
6.74 (d, J¼8.6 Hz, 8H), 7.00 (d, J¼8.8 Hz, 8H), 7.38 (s, 1H); 13C NMR
d
¼32.5, 48.7, 109.0, 118.1 (q), 118.7, 119.8, 121.5,
(50 MHz, CDCl3):
d
¼48.8 (2C), 55.0 (4C), 107.5 (2C), 113.5 (8C), 129.5
126.0, 127.3 (q), 128.1, 128.6, 128.9, 137.3 (q), 144.0 (2C, q); MS (EI):
(8C), 133.8 (q, 2C), 135.5 (q, 4C), 158.0 (q, 4C); calcd for C34H33NO4: C
78.59%; H 6.40%; N 2.70%, found: C 78.50%; H 6.45%; N 2.73%.
m/z (%) 297 [Mþ](80), 220 (100).
4.2.11. Bis(4-fluorophenyl)(2,4,5-trimethoxyphenyl)methane
(7a).5 Chromatographic eluent: CH2Cl2; white solid (0.35 g, 95%
4.2.5. Bis(4-methoxyphenyl)(1-methyl-3-indolyl)methane
(4e).5,18 Chromatographic eluent: PE/AcOEt¼9:1; white solid
yield); mp 126.5e127.5 ꢀC (CH2Cl2/PE) [lit. 126e127 ꢀC]; IR
n
(0.34 g, 94% yield); mp 105e106 ꢀC (CH2Cl2/PE) [lit. 116e117 ꢀC]; IR
n
(cmꢂ1): 3030, 2937, 2833, 1598, 1505, 1202, 1157, 1031, 853, 820,
759; 1H NMR (200 MHz, CDCl3):
¼3.56 (s, 3H), 3.62 (s, 3H), 3.83 (s,
3H), 5.74 (s, 1H), 6.30 (s, 1H), 6.49 (s, 1H), 6.83e7.05 (m, 8H); 13C
NMR (50 MHz, CDCl3):
(cmꢂ1): 3023, 2954, 2828, 1606, 1505, 1242, 1171, 1028, 811, 746; 1H
NMR (200 MHz, CDCl3):
¼3.66 (s, 3H), 3.77 (s, 6H), 5.57 (s, 1H), 6.40
(s, 1H), 6.82 (d, J¼8.6 Hz, 4H), 6.90e7.01 (m, 1H), 7.10e7.30 (m, 7H);
13C NMR (50 MHz, CDCl3):
d
d
d
¼47.6, 55.9, 56.4, 56.5, 97.8, 114.3, 114.8 (d, J
d
¼32.5, 46.9, 55.0 (2C), 108.9, 113.4 (4C),
(C,F)¼21 Hz),123.7 (q), 130.4 (d, J (C,F)¼7.5 Hz, 2C), 139.4 (q, J (C,F)¼
3.0 Hz, 2C), 142.7 (q), 148.3 (q), 151.2 (q), 161.1 (q, J (C,F)¼243 Hz,
2C); MS (EI): m/z (%) 370 [Mþ](100), 355 (30), 339 (35).
118.6, 118.8 (q), 119.9, 121.4, 127.2 (q), 128.4, 129.6 (4C), 136.5 (q, 2C),
137.3 (q), 157.7 (q, 2C); MS (EI): m/z (%) 357 [Mþ](100), 250 (90).
4.2.6. Bis(4-dimethylaminophenyl)(2-pyrrolyl)methane
(5a). Chromatographic eluent: PE/AcOEt¼8:2; oil (0.15 g, 48%
4.2.12. Bis(4-fluorophenyl)(1-methyl-3-indolyl)methane
(7b).18 Chromatographic eluent: PE/AcOEt¼9:1; yellow oil (0.26 g,

M. Barbero et al. / Tetrahedron 70 (2014) 1818e1826
1825
78% yield); IR
699; 1H NMR (200 MHz, CDCl3):
1H), 6.85e7.00 (m, 5H), 7.05e7.29 (m, 7H); 13C NMR (50 MHz,
CDCl3):
118.8, 119.6, 121.6, 126.9 (q), 128.4, 130.1 (d, J (C,F)¼8 Hz, 2C), 137.3
(q), 139.5 (q, J (C,F)¼3 Hz, 2C), 161.3 (q, J (C,F)¼243 Hz, 2C); MS (EI):
m/z (%) 333 [Mþ](75), 238 (100).
n
(cmꢂ1): 2937, 2828,1601,1507,1451,1202,1033, 841,
¼3.67 (s, 3H), 5.59 (s, 1H), 6.33 (s,
1036, 1019, 782; 1H NMR (200 MHz, CDCl3):
d¼2.21 (s, 3H), 3.75 (s,
d
3H), 3.82 (s, 2H), 5.78e5.85 (m, 2H), 6.80 (d, J¼8.6 Hz, 2H), 7.12 (d,
J¼8.8 Hz, 2H); 13C NMR (50 MHz, CDCl3):
¼13.4, 33.5, 55.1, 105.8,
d
d
¼32.5, 47.1, 109.1, 114.9 (d, J (C,F)¼21 Hz, 2C), 117.9 (q),
106.5, 113.7 (2C), 129.5 (2C), 130.4 (q), 150.7 (q), 153.0 (q), 158.0 (q);
MS (EI): m/z (%) 202 [Mþ](100), 187 (40), 171 (40).
4.2.18. (4-Methoxyphenyl)(1-methyl-3-indolyl)methane
(9c).35 Chromatographic eluent: PE/AcOEt¼8:2; oil (0.12 g, 48%
4.2.13. (4-Dimethylaminophenyl)(2,4,5-trimethoxyphenyl)phenyl-
yield); IR n
(cmꢂ1): 2954, 2833, 1606, 1510, 1257, 1080, 1011, 791; 1H
methane (8a). Chromatographic eluent: PE/EE¼9:1; white solid
NMR (200 MHz, CDCl3):
6.69 (s, 1H), 6.78 (d, J¼8.6 Hz, 2H), 6.90e7.28 (m, 5H), 7.35e7.53 (m,
1H); 13C NMR (50 MHz, CDCl3):
d
¼3.63 (s, 3H), 3.74 (s, 3H), 4.00 (s, 2H),
(0.19 g, 50% yield); mp 112e113 ꢀC (EtOH); IR (cmꢂ1): 3023, 2953,
n
2894, 2825, 1606, 1510, 1202, 1180, 1048, 1034, 813; 1H NMR
(200 MHz, CDCl3):
d
¼30.5, 32.4, 55.1, 109.0, 113.6 (2C),
d
¼2.87 (s, 6H), 3.61 (s, 3H), 3.63 (s, 3H), 3.84 (s,
114.6 (q), 118.6, 119.1, 121.4, 126.9 (q), 127.7, 129.7 (2C), 133.4 (q),
3H), 5.76 (s, 1H), 6.46 (s, 1H), 6.50 (s, 1H), 6.74 (d, J¼8.8 Hz, 2H), 6.94
137.1 (q), 157.7 (q); MS (EI): m/z (%) 251 [Mþ](100), 144 (58).
(d, J¼8.8 Hz, 2H), 6.90e7.25 (m, 5H); 13C NMR (50 MHz, CDCl3):
d
¼40.6 (2C), 48.0, 55.9, 56.5, 56.7, 98.0, 112.4 (2C), 114.6, 125.0 (q),
4 . 2 .19 . 1 - P h e n yl - 1 - ( 2 , 4 , 5 - t r i m e t h o x y p h e n y l ) e t h a n e
125.6,127.8 (2C),129.1 (2C),129.8 (2C),132.0 (q),142.6 (q),144.8 (q),
147.8 (q), 148.7 (q), 151.2 (q); MS (EI): m/z (%) 377 (Mþ, 100), 300
(45); calcd for C24H27NO3: C 76.36%; H 7.21%; N 3.71%, found: C
76.27%; H 7.16%; N 3.65%.
(13a). Chromatographic eluent: PE/AcOEt¼7:3; oil (0.22 g, 82%
yield); IR n
(cmꢂ1): 3052, 2925, 1601, 1503, 1218, 1154, 820, 738; 1H
NMR (200 MHz, CDCl3):
(s, 3H), 3.82 (s, 3H), 4.47 (q, J¼7.2 Hz, 1H), 6.47 (s, 1H), 6.67 (s, 1H),
7.15e7.25 (m, 5H); 13C NMR (50 MHz, CDCl3):
d¼1.52 (d, J¼7.4 Hz, 3H), 3.69 (s, 3H), 3.73
d
¼20.8, 36.8, 56.0,
4.2.14. (4-Dimethylaminophenyl)(2-pyrrolyl)phenylmethane
56.5, 56.6, 98.0, 112.2, 125.5, 126.5 (q), 127.3 (2C), 127.9 (2C), 142.9
(q), 146.4 (q), 147.7 (q), 150.9 (q); MS (EI): m/z (%) 272 [Mþ](100),
257 (95), 91 (30); calcd for C17H20O3: C 74.97%; H 7.40%, found: C
74.87%; H 7.36%%.
(8b).33 Chromatographic eluent: PE/EE¼7:3; solid (0.15 g, 53%
yield); mp 84.5e86 ꢀC (CH2Cl2/PE); IR
n
(cmꢂ1): 3391, 2879, 1612,
1523, 1353, 1025, 799, 781, 736, 726, 698; 1H NMR (200 MHz,
CDCl3):
d
¼2.89 (s, 6H), 5.35 (s, 1H), 5.75e5.79 (m, 1H), 6.10e6.15
(m, 1H), 6.66 (d, J¼8.6 Hz, 2H) overlapped with 6.62e6.65 (m, 1H),
4.2.20. 1-(4-Methoxyphenyl)-1-(2,4,5-trimethoxyphenyl)ethane
7.03 (d, J¼8.6 Hz, 2H), 7.13e7.29 (m, 5H), 7.78 (br s, 1H); 13C NMR
(14a). Chromatographic eluent: PE/AcOEt¼7:3; oil (0.20 g, 67%
(50 MHz, CDCl3):
d
¼40.7 (2C), 49.6, 107.6, 108.0, 112.7 (2C), 116.9,
yield); IR n
(cmꢂ1): 2955, 2928, 2832, 1610, 1506, 1453, 1243, 1201,
126.4,128.4 (2C),128.8 (2C),129.5 (2C),131.1 (q),134.4 (q),143.9 (q),
1175,1031, 831; 1H NMR (200 MHz, CDCl3):
d
¼1.48 (d, J¼7.2 Hz, 3H),
149.3 (q); MS (EI): m/z (%) 276 (Mþ, 100), 199 (80).
3.69 (s, 3H), 3.71 (s, 3H), 3.72 (s, 3H), 3.81 (s, 3H), 4.42 (q, J¼7.2 Hz,
As reported in the results and discussion section, 2,5-bis[(4-
dimethylaminophenyl)phenyl-methyl]pyrrole was isolated as
a dialkylation product; solid (0.13 g, 27% yield); mp 48e50 ꢀC
1H), 6.46 (s,1H), 6.64 (s,1H), 6.76 (d, J¼8.8 Hz, 2H), 7.10 (d, J¼8.8 Hz,
2H); 13C NMR (50 MHz, CDCl3):
98.0, 112.1, 113.3 (2C), 126.9 (q), 128.2 (2C), 138.5 (q), 142.9 (q), 147.6
(q),150.8 (q),157.4 (q); MS (EI): m/z (%) 302 [Mþ](78), 287 (100),121
(48); calcd for C18H22O4: C 71.50%; H 7.33%, found: C 71.47%; H 7.26%.
d
¼21.0, 36.0, 55.0, 56.0, 56.5, 56.6,
(EtOH);33 IR
696; 1H NMR (200 MHz, CDCl3):
J¼2.8 Hz, 2H), 6.62 (d, J¼8.6 Hz, 4H), 6.98 (d, J¼8.6 Hz, 4H), 7.09e7.24
(m, 10H), 7.43 (br s, 1H); 13C NMR (50 MHz, CDCl3):
40.6 (4C), 49.5
n
(cmꢂ1): 3437, 3264, 2788, 1608, 1509, 1210, 815, 725,
d¼2.86 (s,12H), 5.22 (s, 2H), 5.54 (d,
d
4 . 2 . 21. 1 - ( 4 - M e t h o x y p h e n y l ) - 1 - ( 3 - i n d o l y l ) e t h a n e
(2C), 107.4 (2C), 112.6 (4C), 126.1 (2C), 128.1 (4C), 128.6 (4C), 129.3
(4C), 133.8 (q, 2C), 143.7 (q, 4C), 148.9 (q, 2C); calcd for C34H34N3: C
84.26%; H 7.07%; N 8.67%, found: C 84.19%; H 7.00%; N 8.65%.
(14b).13,21 Chromatographic eluent: PE/AcOEt¼9:1; solid (0.16 g,
66% yield); mp 140.5e141.5 ꢀC (CH2Cl2/PE) [lit. 137e140 ꢀC];13 IR
n
(cmꢂ1): 3408, 3362, 2956, 1612, 1508, 1457, 1237, 1176, 1023, 829,
742; 1H NMR (200 MHz, CDCl3):
3H), 4.29 (q, J¼7.0 Hz, 1H), 6.77 (d, J¼8.8 Hz, 2H), 6.91e7.00 (m, 2H),
d
¼1.64 (d, J¼7.2 Hz, 3H), 3.73 (s,
4.2.15. (4-Dimethylaminophenyl)(1-methyl-3-indolyl)phenyl-
methane (8c).34 Chromatographic eluent: PE/AcOEt¼8:2; white
solid (0.32 g, 94% yield); mp 160e161 ꢀC (CH2Cl2/PE) [lit.
7.06e7.20 (m, 3H), 7.25e7.35 (m, 2H), 7.87 (br s, 1H); 13C NMR
(50 MHz, CDCl3):
d
¼22.4, 35.9, 55.1, 110.8, 113.5 (2C), 119.0, 119.6,
139e141 ꢀC]; IR
n
(cmꢂ1): 3030, 2954, 2787, 1609, 1513, 1327, 1127,
120.8, 121.6 (q), 121.7, 126.7 (q), 128.1 (2C), 136.5 (q), 138.9 (q), 157.6
735, 698; 1H NMR (200 MHz, CDCl3):
d¼2.89 (s, 6H), 3.65 (s, 3H),
(q); MS (EI): m/z (%) 251 [Mþ](43), 236 (100).
5.55 (s, 1H), 6.40 (s, 1H), 6.66 (d, J¼8.6 Hz, 2H), 6.93 (t, J¼7.6 Hz,1H),
7.07 (d, J¼8.8 Hz, 2H), 7.10e7.28 (m, 8H); 13C NMR (50 MHz, CDCl3):
4.2.22. 1-(4-Methoxyphenyl)-1-(2-methyl-3-indolyl)ethane
d
¼32.5, 40.7 (2C), 47.7, 108.9, 112.5, 118.5, 118.8 (q), 120.0, 121.3,
(14c).21 Chromatographic eluent: PE/AcOEt¼9:1; solid (0.25 g, 73%
125.7, 127.3 (q), 128.0, 128.5, 128.8, 129.4, 137.3 (q), 144.7 (q), 148.7
yield); mp 89e90.5 ꢀC (CH2Cl2/PE); IR (cmꢂ1): 3402, 3322, 2971,
n
(q); MS (EI): m/z (%) 340 [Mþ](100), 363 (90).
1673, 1609, 1508, 1459, 1240, 1176, 1029, 829, 741; 1H NMR
(200 MHz, CDCl3):
d
¼1.73 (d, J¼7.4 Hz, 3H), 2.29 (s, 3H), 3.74 (s, 3H),
4.2.16. (2,4,5-Trimethoxyphenyl)(4-methoxyphenyl)methane
4.36 (q, J¼7.2 Hz, 1H), 7.79 (d, J¼8.6 Hz, 2H), 6.90e7.05 (m, 2H),
(9a).35 Chromatographic eluent: PE/AcOEt¼8:2; low melting point
7.18e7.28 (m, 3H), 7.33e7.40 (m, 1H), 7.68 (br s, 1H); 13C NMR
solid (0.25 g, 86% yield); IR
n
(cmꢂ1): 3030, 2931, 2839, 1609, 1507,
(50 MHz, CDCl3):
d
¼12.0, 20.6, 34.4, 55.1, 110.1, 113.3 (2C), 116.1 (q),
1465,1222, 1202, 1027, 859, 805; 1H NMR (200 MHz, CDCl3):
d
¼3.72
118.8, 119.2,120.5,127.6 (q), 128.1 (2C),130.3 (q), 135.2 (q),138.2 (q),
(s, 6H), 3.73 (s, 3H), 3.81 (s, 2H), 3.83 (s, 3H), 6.49 (s, 1H), 6.59 (s,
157.3 (q); MS (EI): m/z (%) 265 [Mþ](48), 250 (100).
1H), 6.76 (d, J¼8.8 Hz, 2H), 7.06 (d, J¼8.8 Hz, 2H); 13C NMR (50 MHz,
CDCl3):
d
¼34.2, 55.0, 56.0, 56.3, 56.4, 97.8, 113.5 (2C), 114.3, 121.4
4.3. Acid-catalysed reaction of (4-dimethylaminophenyl)
phenylmethanol (2e): synthesis of bis(4-
dimethylaminophenyl)phenylmethane (16) and bis[(4-
dimethylaminophenyl)phenyl-methyl] ether (17)
(q), 129.4 (2C), 133.3 (q), 142.8 (q), 147.8 (q), 151.2 (q), 157.5 (q); MS
(EI): m/z (%) 288 [Mþ](100), 273 (30), 257 (28).
4. 2.17. (4-Methoxyphenyl)(5-methyl-2-furyl)methane
(9b).36 Chromatographic eluent: PE/AcOEt¼8:2; oil (0.13 g, 65%
A mixture of (4-dimethylaminophenyl)phenylmethanol (2e,
0.23 g; 1.0 mmol) and o-benzenedisulfonimide (1, 5 mol %, 0.011 g)
yield); IR
n
(cmꢂ1): 3030, 2914, 1710, 1606, 1566, 1510, 1246, 1175,

1826
M. Barbero et al. / Tetrahedron 70 (2014) 1818e1826
in toluene (2 mL) was stirred at rt in a vial until TLC, GC and GCeMS
analyses shown no further 2e conversion (about 48 h). Other re-
action conditions (temperatures and times) were tested, but an
almost invariable ratio of 16 and 17 in the reaction mixture was
shown by 1H NMR spectroscopy. The reaction mixture was then
treated with CH2Cl2/H2O (1:1, 20 mL). The aqueous phase was
extracted with CH2Cl2 (2ꢁ20 mL). The combined organic extracts
were dried with Na2SO4 and concentrated under reduced pressure.
The crude residue was purified by column chromatography (silica
gel, PE/Acetone¼8:2); the first eluted product was pure 16, the
second one 17.
Supplementary data
1H and 13C NMR spectra for products 4e14 and 16e18 are
available. Supplementary data related to this article can be found at
http://dx.doi.org/10.1016/j.tet.2014.01.011.
References and notes
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4.3.1. Bis(4-dimethylaminophenyl)phenylmethane (16).37 Light blue
solid (0.04 g, 25% yield); mp 99e100 ꢀC (CH2Cl2/PE) [lit.
105.5e107 ꢀC]38; IR
n
(cmꢂ1): 3030, 2873, 2810, 1611, 1518, 1348,
1224, 786, 699; 1H NMR (200 MHz, CDCl3):
1H), 6.64 (d, J¼8.8 Hz, 4H), 6.96 (d, J¼9.0 Hz, 4H), 7.09e7.28 (m,
5H); 13C NMR (50 MHz, CDCl3):
d¼2.88 (s, 12H), 5.36 (s,
d¼40.6 (4C), 54.8, 112.4 (4C), 125.6,
127.9 (2C), 129.2 (2C), 129.8 (4C), 132.7 (q), 145.3 (q), 148.8 (q, 2C);
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4.3.2. Bis[(4-dimethylaminophenyl)phenylmethyl] ether (17). White
solid (0.10 g, 46% yield); mp 85.5e87 ꢀC (CH2Cl2/PE); di-
astereomeric mixture; IR
n
(cmꢂ1): 2850, 2799, 1606, 1518, 1340,
1160,1031, 804, 753, 719, 695; 1H NMR (200 MHz, CDCl3):
d
¼2.91 (s,
12H), 5.34 (s, 2H), 6.69 (d, J¼8.8 Hz, 4H), 7.18e7.45 (m, 14H); 13C
NMR (50 MHz, CDCl3):
d¼40.5 (6C), 79.1, 79.3, 112.2 (4C), 126.7,
126.8, 126.9 (2C), 127.0 (2C), 128.0 (2C), 128.1 (2C), 128.3 (2C), 128.5
(2C), 129.9 (q), 130.4 (q), 142.9 (q), 143.4 (q), 149.7 (q), 149.8 (q); MS
(ESIþ): m/z 437.53 [MþH]þ; calcd for C30H32N2O: C 82.52%; H
7.39%; N 6.42%, found: C 82.55%; H 7.30%; N 6.50%.
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A mixture of indole (3f; 0.23 g; 2.0 mmol) and o-benzenedi-
sulfonimide (1, 10 mol %, 0.044 g) was stirred in a vial at 60 ꢀC for
5 h. The reaction mixture was then treated with CH2Cl2/H2O (1:1,
20 mL). The aqueous phase was extracted with CH2Cl2
(2ꢁ20 mL). The combined organic extracts were dried with
Na2SO4 and concentrated under reduced pressure. The crude
residue was purified by column chromatography (silica gel, PE/
AcOEt¼1:1). Product 18 was obtained as a solid (0.14 g, 61%
yield); mp 156e157 ꢀC (CH2Cl2/PE) [lit. 163e164 ꢀC];39 IR
n
(cmꢂ1): 3404, 3052, 1617, 1495, 1455, 1094, 1012, 740; 1H NMR
(200 MHz, CDCl3):
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2H), 7.68 (br s, 2H); 13C NMR (50 MHz, CDCl3):
d
¼34.1, 37.0, 111.1
(2C), 115.6, 118.7, 118.9 (2C), 119.2 (q, 2C), 119.4 (2C), 121.6 (2C),
121.9 (2C), 125.9 (q), 127.7 (overlapped with q, 3C), 130.1, 136.4 (q,
2C), 144.5.
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Acknowledgements
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ꢀ
This work was supported by Italian MIUR and by Universita
degli Studi di Torino.
39. Aburatani, S.; Uenishi, J. Heterocycles 2008, 75, 1407e1416.