Alkylation of arenes with benzylic and propargylic alcohols - Classical versus fancy catalysts

Article abstract of DOI:10.1002/adsc.200505411

Gold chloride and BF₃ · etherate were tested as Friedel-Crafts catalysts in the propargylation of electron-rich arenes: differences in reactivity of the catalysts can be used to achieve high selectivity either for monoalkylation or for multiple

Full text of DOI:10.1002/adsc.200505411

FULL PAPERS
DOI: 10.1002/adsc.200505411
Alkylation of Arenes with Benzylic and Propargylic
Alcohols -- Classical versus Fancy Catalysts
Jianhui Liu,a Enrico Muth,a Ulrich Flçrke,b Gerald Henkel,b Klaus Merz,a
Janelle Sauvageau,a Erik Schwake,a Gerald Dykera,*
a
Fakultät für Chemie, Ruhr-Universität Bochum, Universitätsstrasse 150, 44780 Bochum, Germany
Fax: (þ49)-234-321-4353, e-mail: Gerald.Dyker@rub.de
b
Universität Paderborn, Fakultät für Naturwissenschaften, Department Chemie, Warburger Str. 100, 33098 Paderborn,
Germany
Received: October 19, 2005; Accepted: December 28, 2005
Supporting Information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: Gold chloride and BF3 ·etherate were tested selectivity, whereas p-toluenesulfonic acid as catalyst
as Friedel–Crafts catalysts in the propargylation of opened up a competing pathway to a structural iso-
electron-rich arenes: differences in reactivity of the mer.
catalysts can be used to achieve high selectivity either
for monoalkylation or for multiple alkylation prod-
ucts. In the case of a macrocyclization towards a het- Keywords: Friedel–Crafts reaction; gold catalysis;
erocalixarene, gold catalysts exhibited a pronounced Lewis acids; macrocycles
Introduction
es[5–7] we became interested in multifold Friedel–Crafts
alkylations including cyclization reactions and tested
Friedel–Crafts alkylations still belong to the most im- the catalytic activity and selectivity of gold(III) chloride
À
portant C C bond-coupling reactions. When alcohols in comparison to classical Friedel–Crafts catalysts.
or even olefins are applied as pre-electrophiles, this
type of reaction is especially attractive from a practical
point of view, profiting from the versatility and the avail- Results and Discussion
ability of the starting materials and from the highly
atom-economical[1] character. However, the fact that For the propargylation of electron-rich arenes we chose
classical Friedel–Crafts catalysts, such as aluminium 1,3-dimethoxybenzene (1), 1,3,5-trimethoxybenzene (5)
chloride or hydrogen chloride, generally are applied in and azulene (8) as model substrates (Scheme 1), since all
at least stoechiometric amounts and are often not com- three compounds have been successfully monoalkylated
patible with sensitive functional groups is regarded as a with propargylic alcohol 2 in the presence of 5% of the
serious drawback. Therefore there is indeed a demand Re or the Ru catalysts mentioned above (reported reac-
for new catalysts exhibiting outstanding activity in com- tion conditions: 1–5 h at about 608C). As a result, just
bination with high selectivity. Recently Uemura et al. 0.3 to 1% of the gold catalyst are sufficient for achieving
reported on a dinuclear cationic ruthenium complex a 96% isolated yield of the monosubstitution products 3
which is exceptional active for the propargylation of and 6. The reaction was performed at room temperature
electron-rich arenes with propargylic alcohols as re- with 2 equivalents of propargylic alcohol 2, thus demon-
agents.[2] In addition, Toste et al.[3] introduced the air- strating both an outstanding reactivity and a remarkable
and moisture-tolerant Re-complex (dppm)Re(O)Cl3 selectivity for the monosubstitution. In the case of the
as an alternative catalyst for the propargylation. For Ru catalyst the selectivity was purchased with the disad-
the benzylation of arenes Beller et al. tested a variety vantage of applying a 5-fold excess of the arenes 1 and 5.
of simple transition metal salts and also some Brønstedt However, with azulene 8 as a somewhat acid-sensitive
acids: iron(III) chloride became the favourite catalyst, arene component the gold catalyst warrants only a mod-
regularly leading to practically quantitative yields.[4] erate yield of monosubstitution product 9, compared to
In the course of our studies on gold-catalyzed process- the 91% reported for the Ru catalyst. Most interestingly,
456
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 456 – 462

Alkylation of Arenes with Benzylic and Propargylic Alcohols
FULL PAPERS
Scheme 1. Propargylation of electron-rich arenes.
the application of the classical Friedel–Crafts catalyst tion product 11 is obtained in a 82% yield. In compari-
BF3 ·etherate in stoichiometric amounts turned out to son, with BF3 ·etherate the yield of 11 drops to less
be the most versatile method for selectively accessing ei- than 1% because of the formation of a complex mixture
ther the mono- or the dialkylation products: thus, 1 of by-products, even with a very short reaction time of
equivalent of propargylic alcohol 2 in combination less than 5 minutes.
with a reaction temperature of 08C and just 5 min reac-
Methylfuran was readily alkylated in the presence of
tion time were the conditions of choice for obtaining an BF3 ·etherate to give 12 in excellent yield (Scheme 2),
optimum of monoalkylation products. Use of 2 equiva- whereas pyrene reacts significantly more sluggishly: a
lents of 2 with 1 h reaction time at room temperature 26% yield of the monoalkylation product 13 was ob-
led to clean formation of the bis-substitution products tained after 1 h reaction time, prompting us to suggest
4 and 7, both as a mixture of the two diastereoisomers this less electron-rich polycyclic arene as a suitable
(4 in the ratio 1:1 and 7 in the ratio 1:2). In the case of benchmark substrate for further studies on the compar-
azulene 8 the bis-product formation was also successful, ison of Friedel–Crafts catalysts.
albeit with only moderate yield. Some other substrates
As a chemical proof of its structure as well as in order
were chosen to evaluate scope and limitations of the to test its reactivity we performed a Pd-catalyzed annu-
propargylation with gold chloride and with BF3 ·ether- lation reaction with the crowded alkyne 6 resulting in
ate as catalysts: in the case of 2,4-dimethoxybenzalde- the formation of the phenanthrene derivative 14
hyde the gold catalyst is clearly superior, since the alde- (Scheme 2).[8]
hyde functionality is tolerated and the monopropargyla-
Adv. Synth. Catal. 2006, 348, 456 – 462
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
457

Jianhui Liu et al.
FULL PAPERS
We became interested in the Friedel–Crafts alkylation
of pyrroles as crucial steps in the synthesis of heteroca-
lixarene 17,[10] which resembles a tetradentate ligand re-
lated to porphyrins. Since the highly reactive pyrrole
tends to polymerize under strongly acidic conditions,[11]
we decided to apply p-toluenesulfonic acid and gold
chloride as catalysts with moderate acidity. Building
block 15 is readily synthesized by the reaction of pyri-
dine-2,6-dicarboxylic acid esters with an excess of ani-
syl-Grignard reagent. The subsequent double condensa-
tion with pyrrole under catalysis by p-toluenesulfonic
acid resulted in the formation of 16 in excellent yield.
The macrocyclization to the target compound 17 pro-
ceeded smoothly with 3% AuCl3 in refluxing acetoni-
trile. Applying 66% tetrachlorogold acid as catalyst
slightly increased the yield to 43%.
Surprisingly, with p-toluenesulfonic acid as the cata-
lyst an unprecedented competing reaction occurred,
which favoured the formation of an isomer: 18 was iden-
tified by X-ray crystal structure analysis (Figure 2).[8]
The single crystals were obtained from dichlorome-
thane/methanol (3:1) in the presence of copper(II) ace-
Scheme 2. Additional products from propargylation reactions
and further transformations.
Single crystals of 4 were obtained by recrystallization tate, which seemed to catalyze the crystallization proc-
of the mixture of diastereoisomers of 4 from methyl tert- ess, but was not incorporated itself into the crystal lat-
butyl ether/petroleum ether. An X-ray crystal analysis[9] tice. The mechanistic rationale for the formation of 18
clearly showed the structure of SS-4 in a centrosymmet- includes the benzylic cations 19 and 20 as reactive inter-
rical space group (Figure 1).
mediates (Scheme 4), the latter being suitable for nucle-
ophilic attack at the pyridine moiety. As a working
hypothesis we assume that, in the case of the gold cata-
lysts, the cyclization to indole 20 is inhibited, because the
pyridine nitrogen might be coordinated to the metal.[12]
Conclusion
In summary, we have proven that gold chloride is a very
mild, yet highly reactive Friedel–Crafts catalyst, which
works already at rather low concentration and ensures
a high selectivity for propargylation and benzylation
reactions. On the other hand, BF3 ·etherate in stoichio-
metric amounts allows us to drive multifold propargyla-
tions to the limit, enabling the synthesis of somewhat
crowded products. Finally, the comparison of p-toluene-
sulfonic acid with gold chloride and with tetrachloro-
gold acid, respectively, as catalysts in a macrocyliza-
tion reaction illustrates surprising differences in se-
lectivity: the reasons should be clarifiedby ongoing stud-
ies.
Experimental Section
General Remarks
Melting points (mp, uncorrected): Reichert Thermovar. IR:
Perkin Elmer 841 and 983. NMR: Bruker DPX-200, WM-
300, DRX-400, AM-500, DRX-600; 1H NMR spectra were re-
Figure 1. Molecular structure of the SS-enantiomer of 4, hy-
drogen atoms omitted for the sake of clarity.
458
asc.wiley-vch.de
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 456 – 462

Alkylation of Arenes with Benzylic and Propargylic Alcohols
FULL PAPERS
Scheme 3. Au-catalyzed macrocyclization and its acid-catalyzed competing reaction.
corded in CDCl3 with TMS as the internal standard (see Sup-
porting Information); 13C NMR spectra were measured by us-
ing CDCl3 as the solvent and the internal standard; assignments
based on analysis of HMBC and HMQC spectra. MS: MAT 700
ITD(70 eV) and Varian MAT 311 A. For analytical TLC pre-
coated plastic sheets “POLYGRAM SIL G/UV254” from
“Macherey-Nagel” were used. Elemental analysis: Elemen-
tar/Hanau Vario EL. Spectroscopic data and elemental analy-
ses for all mew compounds are presented in the Supporting In-
formation.
Scheme 4. Reactive intermediates of the formation of 18.
2,4-Dimethoxy-1-(1,3-diphenylpropyn-3-yl)-benzene
(3)
A mixture of 208 mg (1.00 mmol) of 1,3-diphenyl-2-propyn-1-
ol (2) and 138 mg (1.00 mmol) of 1,3-dimethoxybenzene (1) in
10 mL of dry acetonitrile under argon was cooled to 08C and a
solution of 142 mg (1.00 mmol) of BF3 ·Et2O in 2 mL of aceto-
nitrile was added under stirring within 1 min. After 5 min stir-
ring at 08C 10 mL of MeCN were added and the mixture was
filtered through 4 g silica. The solvent was removed under vac-
uum and the residue was purified by flash chromatography
(10 g of silica, petrol ether/methyl tert-butyl ether, 2:1, Rf ¼
0.16, 0.00). The fraction with Rf ¼0.16 was isolated and dried
under vacuum (0.2 mbar, 508C); yield of 3:[2,3] 311 mg (95%);
colourless crystals with mp 1178C.
Figure 2. Molecular structure of 18, hydrogen atoms omitted
for the sake of clarity.
Adv. Synth. Catal. 2006, 348, 456 – 462
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
459

Jianhui Liu et al.
FULL PAPERS
through 4 g silica. The solvent was removed under vacuum
and the residue was purified by flash chromatography (10 g
of silica, petrol ether/methyl tert-butyl ether, 2:1, Rf ¼0.14,
0.00). The fraction with Rf ¼0.14 was isolated and dried under
vacuum (0.2 mbar, 508C) to afford 9;[2] yield: 117 mg (54%);
dark blue crystals; mp 1138C.
2,4-Bis-(1,3-diphenylpropyn-3-yl)-1,5-
dimethoxybenzene (4)
A mixture of 416 mg (2.00 mmol) of 1,3-diphenyl-2-propyn-1-
ol (2) and 138 mg (1.00 mmol) of 1,3-dimethoxybenzene (1) in
10 mL of dry acetonitrile under argon was cooled to 08C and a
solution of 284 mg (2.00 mmol) of BF3 ·Et2O in 2 mL of aceto-
nitrile was added under stirring within 1 min. After 1 h stirring
at room temperature 10 mL of MeCN were added and the mix-
ture was filtered through 4 g silica. The solvent was removed
under vacuum and the residue was purified by flash chroma-
tography (10 g of silica, petrol ether/methyl tert-butyl ether,
2:1, Rf ¼0.10, 0.00). The fraction with Rf ¼0.10 was isolated
and dried under vacuum (0.2 mbar, 508C) to afford a colorless
solid with mp 158–1598C, which was identified as a 1:1 mix-
ture of the diastereoisomers of 4; yield: 493 mg (95%). Single
crystals of the pure isomers are obtained by recrystallization
from petrol ether/methyl tert-butyl ether (2:1).
1,3-Bis-(1,3-diphenylpropyn-3-yl)-azulene (10)
A mixture of 416 mg (2.00 mmol) of 1,3-diphenyl-2-propyn-1-
ol (2) and 128 mg (1.00 mmol) of azulene (8) in 10 mL of dry
acetonitrile under argon was cooled to 08C and a solution of
284 mg (2.00 mmol) of BF3 ·Et2O in 2 mL of acetonitrile was
added under stirring within 1 min. After 1 h stirring at room
temperature 10 mL of MeCN were added and the mixture
was filtered through 4 g silica. The solvent was removed under
vacuum and the residue was purified by flash chromatography
(10 g of silica, petrol ether/methyl tert-butyl ether, 2:1, Rf ¼
0.11, 0.00). The fraction with Rf ¼0.11 was isolated and dried
under vacuum (0.2 mbar, 508C) to afford dark blue crystals
with mp. 1488C, which were identified as a 1:1 mixture of
the diastereoisomers of 10; yield:147 mg (29%).
2-(1,3-Diphenylpropyn-3-yl)-1,3,5-trimethoxybenzene
(6)
A mixture of 208 mg (1.00 mmol) of 1,3-diphenyl-2-propyn-1-
ol (2) and 168 mg (1.00 mmol) of 1,3,5-trimethoxybenzene (5)
in 10 mL of dry acetonitrile under argon was cooled to 08C and
a solution of 142 mg (1.00 mmol) of BF3 ·Et2O in 2 mL of ace-
tonitrile was added under stirring within 1 min. After 5 min
stirring at 08C 10 mL of MeCN were added and the mixture
was filtered through 4 g silica. The solvent was removed under
vacuum and the residue was purified by flash chromatography
(10 g of silica, petrol ether/methyl tert-butyl ether, 2:1, Rf ¼
0.14, 0.00). The fraction with Rf ¼0.14 was isolated and dried
under vacuum (0.2 mbar, 508C) to afford 5;[2] yield: 350 mg
(98%); colourless crystals; mp 1218C.
2,4-Dimethoxy-5-(1,3-diphenylpropyn-3-yl)-
benzaldehyde (11)
A mixture of 208 mg (1.00 mmol) of 1,3-diphenyl-2-propyn-1-
ol and 166 mg (1.00 mmol) of 1,3-dimethoxybenzaldehyde in
10 mL of dry acetonitrile under argon was stirred at room tem-
perature in a sealed tube for 3 days with 3 mg (10 mmol) of
AuCl3 as catalyst (1%). The solvent was evaporated and the res-
idue was purified by flash chromatography (10 g of silica, pet-
rol ether/methyl tert-butyl ether, 2:1, Rf ¼0.12, 0.00). The frac-
tion with Rf ¼0.12 was isolated and dried under vacuum to af-
ford 11; yield: 297 mg (82%); slightly yellow crystals; mp 142–
1458C.
2,4-Bis(1,3-diphenylpropyn-3-yl)-1,3,5-
trimethoxybenzene (7)
A mixture of 416 mg (2.00 mmol) of 1,3-diphenyl-2-propyn-1-
ol (2) and 168 mg (1.00 mmol) of 1,3,5-trimethoxybenzene (5)
in 10 mL of dry acetonitrile under argon was cooled to 08C and
a solution of 284 mg (2.00 mmol) of BF3 ·Et2O in 2 mL of ace-
tonitrile was added under stirring within 1 min. After 1 h stir-
ring at room temperature 10 mL MeCN were added and the
mixture was filtered through 4 g silica. The solvent was re-
moved under vacuum and the residue was purified by flash
chromatography (10 g of silica, petrol ether/methyl tert-butyl
ether, 2:1, Rf ¼0.11, 0.00). The fraction with Rf ¼0.11 was iso-
lated and dried under vacuum (0.2 mbar, 508C) to afford color-
less crystals with mp 1678C, which were identified as a 1:2 mix-
ture of the diastereoisomers of 5; yield: 521 mg (95%).
2-(1,3-Diphenylpropyn-3-yl)-5-methylfuran (12)
A mixture of 208 mg (1.00 mmol) of 1,3-diphenyl-2-propyn-1-
ol (2) and 411 mg (5.00 mmol) of 2-methylfuran in 10 mL of dry
acetonitrile under argon was cooled to 08C and a solution of
142 mg (1.00 mmol) of BF3 ·Et2O in 2 mL of acetonitrile was
added under stirring within 1 min. After 5 min stirring at 08C
10 mL of MeCN were added and the mixture was filtered
through 4 g silica. The solvent was removed under vacuum
and the residue was purified by flash chromatography (10 g
of silica, petrol ether/methyl tert-butyl ether, 2:1, Rf ¼0.18,
0.00). The fraction with Rf ¼0.18 was isolated and dried under
vacuum (0.2 mbar, 508C) to afford 12;[2] yield: 247 mg (91%);
slightly yellowish oil.
1-(1,3-Diphenylpropyn-3-yl)-azulene (9)
1-(1,3-Diphenylpropyn-3-yl)-pyrene (13)
A mixture of 208 mg (1.00 mmol) of 1,3-diphenyl-2-propyn-1-
ol (2) and 128 mg (1.00 mmol) of azulene (8) in 10 mL of dry
acetonitrile under argon was cooled to 08C and a solution of
142 mg (1.00 mmol) of BF3 ·Et2O in 2 mL of acetonitrile was
added under stirring within 1 min. After 5 min stirring at 08C
10 mL of MeCN were added and the mixture was filtered
A mixture of 208 mg (1.00 mmol) of 1,3-diphenyl-2-propyn-1-
ol (2) and 202 mg (1.00 mmol) of pyrene in 10 mL of dry aceto-
nitrile under argon was cooled to 08C and a solution of 142 mg
(1.00 mmol) of BF3 ·Et2O in 2 mL of acetonitrile was added un-
der stirring within 1 min. After 1 h stirring at room tempera-
460
asc.wiley-vch.de
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 456 – 462

Alkylation of Arenes with Benzylic and Propargylic Alcohols
FULL PAPERS
ture 10 mL of MeCN were added and the mixture was filtered
through 4 g silica. The solvent was removed under vacuum and
the residue was purified by flash chromatography (10 g of sili-
ca, petrol ether/methyl tert-butyl ether, 2:1, Rf ¼0.14, 0.00).
The fraction with Rf ¼0.14 was isolated and dried under vac-
uum (0.2 mbar, 508C) to afford 13; yield: 102 mg (26%); pale
yellow crystals; mp 1548C.
phy and crystallized from methanol (5 mL) to give pure 16;
yield: 600 mg (91%); colourless crystals: mp 2188C.
2,2,4,4,6,6,8,8-Octakis(4-methoxyphenyl)-
1,5(2,6)dipyridina-3,7(2,5)-dipyrrolacyclooctaphane
(17)
A mixture of 15 (84 mg, 0.15 mmol), 16 (99 mg, 0.15 mmol) and
tetrachlorogold acid (30 mg, 0.1 mmol) in MeCN (2 mL) was
refluxed at 1208C for 1 h resulting in the formation of a crystal-
line precipitate. TLC of the crude product (petroleum ether/
EtOAc, 2:1; silica): Rf ¼0.37, 0.24. The fraction with Rf ¼
0.24 was isolated by flash chromatography (eluent: petrol
ether/EtOAc, 4:1) to give the macrocycle 17; yield: 77 mg
(43%); yellow solid; mp 242–2438C.
9-Phenyl-10-[phenyl-(2,4,6-trimethoxyphenyl)-
methyl]phenanthrene (14)
A mixture of 816 mg (4.00 mmol) of iodobenzene, 358 mg
(1.00 mmol) of propyne 6, 1.11 g (8.00 mmol) of potassium car-
bonate, 645 mg (2.00 mmol) of tetra-n-butylammonium bro-
mide, 12 mg (50 mmol) of palladium acetate and 26 mg
(100 mmol) of triphenylphosphane in 10 mL of dry DMF was
heated for 3 d under argon at 1008C in a screw-capped tube.
After addition of 50 mL of water and extraction with diethyl
ether (3ꢀ50 mL) the combined organic layer was filtered
through silica (4 g). The solvent was removed under vacuum
and the residue was purified by flash chromatography (10 g
of silica, petrol ether/methyl tert-butyl ether, 2:1, Rf ¼0.11,
0.00). The fraction with Rf ¼0.11 was isolated and dried under
vacuum (0.2 mbar, 508C) to afford 14; yield: 133 mg (26%);
pale yellow crystals; mp 1848C.
Heterocyclophane 18
A chloroform solution (6.5 mL) of 15 (338 mg, 600 mmol), 16
(397 mg, 600 mmol) and p-toluenesulfonic acid hydrate
(114 mg, 600 mmol) was heated at 808C for 1.5 h (under TLC
control). The reaction mixture was washed with water, extract-
ed with CH2Cl2, dried with sodium sulfate and concentrated
under vacuum. TLC of the crude product (petroleum ether/
EtOAc, 3:1; silica): Rf ¼0.55, 0.36. The fraction with Rf ¼
0.36 was isolated by flash chromatography (eluent: petroleum
ether/EtOAc, 4:1) and recrystallized from MeCN (4 mL), the
yellow precipitate was collected and identified as macrocycle
17 by 1H NMR; yield: 200 mg (28%).
The filtrate was concentrated and the residue solidified after
addition of 1 mL of methanol to give 18; yield: 400 mg (56%);
slightly yellow crystals; mp 1908C. Crystals suitable for X-ray
crystal structure analysis were obtained by crystallization
from dichloromethane/methanol (3:1) in the presence of cop-
per acetate.
2,6-Bis[1,1-bis(4-methoxyphenyl)-1-
hydroxymethyl]pyridine (15):
A mixture of magnesium (1.94 g, 80.0 mmol), 4-bromoanisole
(11 mL 88 mmol) and iodine (50 mg) in freshly distilled THF
(50 mL) was stirred under reflux for 15 min at 808C until all
of the magnesium had reacted. After cooling down to 08C, sol-
id dimethyl 2,6-pyridinedicarboxylate (3.12 g, 16.0 mmol) was
added in 5 portions. The reaction mixture was allowed to warm
to room temperature and was then refluxed at 808C for 1 h. At
room temperature a 1 N aqueous solution of ammonium chlor-
ide (40 mL) was added, and the water layer was extracted with
diethyl ether (2ꢀ50 mL). The combined organic layer was
washed with water (2ꢀ50 mL) and brine (50 mL), dried with
sodium sulfate and concentrated under vacuum. TLC of the
crude product (petroleum ether/EtOAc 4:1, silica): Rf ¼0.71,
0.58, 0.09. The fraction with Rf ¼0.09 was isolated by flash
chromatography (silica gel; petrol ether/EtOAc, 2:1) to give
15; yield: 8.00 g (89%); colourless crystals; mp 140–1418C.
Acknowledgements
We gratefully acknowledge financial support from Fonds der
Chemischen Industrie and from the Deutsche Forschungsge-
meischaft (DFG-project DY 12/7–2).
References and Notes
[1] a) B. M. Trost, Science 1991, 254, 1471–1477; b) M. Ban-
dini, M. Fagioli, A. Umani-Ronchi, Adv. Synth. Catal.
2004, 346, 545–548.
[2] Y. Nishibayashi, Y. Inada, M. Yoshikawa, M. Hidai, S.
Uemura, Angew. Chem. Int. Ed. 2003, 42, 1495–1498.
[3] J. J. Kennedy-Smith, L. A. Young, F. D. Toste, Org. Lett.
2004, 6, 1325–1327.
[4] a) I. Iovel, K. Mertins, J. Kischel, A. Zapf, M. Beller, An-
gew. Chem. Int. Ed. 2005, 44, 3913–3917; b) K. Mertins,
I. Iovel, J. Kischel, A. Zapf, M. Beller, Angew. Chem.
Int. Ed. 2005, 44, 238–242.
[5] a) G. Dyker, E. Muth, A. S. K. Hashmi, L. Ding, Adv.
Synth. Catal. 2003, 345, 1247–1252; b) G. Dyker, D. Hil-
debrandt, J. Org. Chem. 2005, 70, 6093–6096.
2,6-Bis[1,1-bis(4-methoxyphenyl)-1-(2-pyrrolyl)-
methyl]pyridine (16)
To a solution of tertiary alcohol 15 (563 mg, 1.00 mmol) and
pyrrole (277 mL, 4.00 mmol) in CH2Cl2 (3 mL) was added p-tol-
uenesulfonic acid hydrate (95 mg, 0.5 mmol). The reaction
mixture was stirred at room temperature for 5.5 h, diluted
with the same solvent (15 mL), washed with water (2ꢀ
15 mL) and with brine (10 mL), dried with sodium sulfate
and concentrated under vacuum. TLC of the crude product
(petroleum ether/EtOAc, 2:1; silica): Rf ¼0.50, 0.31, 0.19.
The fraction with Rf ¼0.50 was isolated by flash chromatogra-
Adv. Synth. Catal. 2006, 348, 456 – 462
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
461

Jianhui Liu et al.
FULL PAPERS
[6] Recent reviews on gold-catalyzed processes: S. K. Hash-
mi, Gold Bulletin 2004, 37, 51–65; b) A. Hoffmann-
Roeder, N. Krause, Org. Biomol. Chem. 2005, 3, 387–
391; c) G. J. Hutchings, Catal. Today 2005, 100, 55–61;
d) C. W. Corti, R. J. Holliday, D. T. Thompson, Appl.
Catalysis, A: General 2005, 291, 253–261.
[7] Related articles on gold catalysis with propargylic alco-
hols and on gold-catalyzed Friedel–Crafts reactions,
see: Georgy, V. Boucard, J.-M. Campagne, J. Am.
Chem. Soc. 2005, 127, 14180–14181; b) Z. Shi, C. He, J.
Am. Chem. Soc. 2004, 126, 5964–5965; c) C. Wei, C.-J.
Li, J. Am. Chem. Soc. 2003, 125, 9584–9585.
modul of PLATON[13] resulted in smooth refinement,
R1 (I>2s(I))¼0.058, wR2 (all data)¼0.154, S¼0.987,
min/max height in final DF-map –0.26/0.48 e/ꢁ3. Struc-
ture solution by direct methods (SHELXS 97), refine-
ment against F2 with all measured reflections
(SHELXTL 97). The positions of the H atoms for rac-4
were calculated, for 18 they were derived from differ-
ence Fourier maps. For both structures H atoms were re-
fined iostropically with a riding model at idealized posi-
tions. Crystallographic data (excluding structure factors)
for the structures reported in this paper have been de-
posited with the Cambridge Crystallographic Data Cen-
tre as supplementary publication no. CCDC 285371 for
rac-4 and CCDC 286814 for 18. Copies of the data can
be obtained free of charge on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK [fax: (þ44)-
1223-336-033; e-mail: deposit@ccdc.cam.ac.uk].
[8] G. Dyker, A. Kellner, Tetrahedron Lett. 1994, 35, 7633–
7636.
[9] Crystal structure analysis: A crystal of rac-4 and 18 were
each mounted on a glass capillary in perflourinated oil
and measured in a cold gas flow. The intensity data
were measured with a Bruker AXS area detector
(MoKa radiation), l¼0.71073 ꢁ, graphite monochroma-
tor. rac-4: (C38H30O2): monoclinic, P21/c, a¼15.268(6),
b¼7.833(2), c¼23.767(9) ꢁ, b¼93.213(7)8, V¼2838(2)
ꢁ3, T¼213 (2) K, Z¼4, m¼1.214 mm–1. A total of
10328 reflections were collected (2qmax ¼50o), 4595 inde-
pendent, 5863 observed (Fo >4s(Fo)), 397 parameters;
R1¼0.0746, wR2 (all data)¼0.2084. 18 (C78H68N4O8 ·
[10] a) V. Kral, J. L. Sessler, T. V. Shishkanova, P. A. Gale, R.
Volf, J. Am. Chem. Soc. 1999, 121, 8771–8775; b) P. A.
Gale, J. L. Sessler, V. Kral, V. Lynch, J. Am. Chem.
Soc. 1996, 118, 5140–5141; c) P. A. Gale, J. L. Sessler,
V. Kral, Chem. Commun. 1998, 1–6; d) P. A. Gale, J. L.
Sessler, V. Kral, V. Lynch, Chem. Commun. 1998, 7–8;
e) J. L. Sessler, P. Anzenbacher, Jr., K. Jursikova, H.
Miyaji, J. W. Genge, N. A. Tvermoes, W. E. Allen, J.
Schriver, P. A. Gale, V. Kral, Pure Appl. Chem. 1998,
70, 2401–2408; f) B. Kçnig, M. Hechavarri Fonseca,
Eur. J. Inorg. Chem. 2000, 2303–2310.
[11] a) D. A. Reece, J. M. Pringle, S. F. Ralph, G. G. Wallace,
Macromolecules 2005, 38, 1616–1622; b) M. L. Kantam,
K. V. S. Ranganath, M. Sateesh, K. B. S. Kumar, B. M.
Choudary, J. Mol. Catal. A: Chemical 2005, 225, 15–20.
[12] A. S. K. Hashmi, J. P. Weyrauch, M. Rudolph, E. Kurpe-
jovic, Angew. Chem. Int. Ed. 2004, 43, 6545–6547.
[13] L. Spek, PLATON, Version 2003, University of Utrecht,
The Netherlands, 2003
¯
2 CH3OH·0.5 CH2Cl2): triclinic, space group P1, a¼
12.5613(6), b¼15.0128(7), c¼19.5558(8) ꢁ, a¼
98.184(1), b¼91.140(1), g¼110.228(1)8, V¼3415.6(3)
ꢁ3, T¼120(2) K, Z¼2, m¼0.12 mm–1. 34447 intensities
collected 1.05>q>28.088, h ꢁ16, k ꢁ19, l ꢁ25, 16489
independent reflections, Rint ¼0.034. The asymmetric
unit contains one molecule of 18 and two methanol sol-
vent molecules. One additional CH2Cl2 solvent molecule
per unit cell was severely disordered showing only dif-
fuse electron density peaks which could not sufficiently
be modelled. Treating the data set with the SQUEEZE
462
asc.wiley-vch.de
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 456 – 462