Practical synthesis of triaryl- and triheteroarylmethanes by reaction of aldehydes and activated arenes promoted by gold(III) chloride

Article abstract of DOI:10.1021/ol052423h

(Chemical Equation Presented) Electron-rich arenes condense efficiently with various aldehydes under the influence of AuCl₃, thus opening up a practical route to triarylmethanes, which have important applications. The mild conditions employed are especially noteworthy.

Full text of DOI:10.1021/ol052423h

ORGANIC
LETTERS
2005
Vol. 7, No. 26
5857-5859
Practical Synthesis of Triaryl- and
Triheteroarylmethanes by Reaction of
Aldehydes and Activated Arenes
Promoted by Gold(III) Chloride
Vijay Nair,* K. G. Abhilash, and N. Vidya
Organic Chemistry DiVision, Regional Research Laboratory (CSIR),
TriVandrum-695019, India
Vijaynair_2001@yahoo.com
Received October 6, 2005
ABSTRACT
Electron-rich arenes condense efficiently with various aldehydes under the influence of AuCl3, thus opening up a practical route to triarylmethanes,
which have important applications. The mild conditions employed are especially noteworthy.
Since the discovery of the triphenylmethyl radical by
Gomberg in 1900,1 triaryl- and triheteroarylmethanes have
Scheme 2. Arene-Aldehyde Condensation
Scheme 1. Heteroarene-Aldehyde Condensation
synthetic, medicinal, and industrial chemistry.2 Inter alia, the
triarylmethyl derivatives are useful as protective groups,3
attracted much attention from organic chemists and many
such compounds have found widespread applications in
(2) (a) Shchepinov, M. S.; Korshun, V. A. Chem. Soc. ReV. 2003, 32,
170. (b) Duxbury, D. F. Chem. ReV. 1993, 93, 381. (c) Schnitzer, R. J.;
Hawking, F. Experimental Chemotherapy; Academic Press: New York,
(1) Gomberg, M. J. Am. Chem. Soc. 1900, 22, 757.
1963; Vol. I.
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Scheme 3. Dialdehyde Condensations
Scheme 4. Toward Dendritic Architectures
photochromic agents,4 and dyes.5 Ring hydroxylated
catalyze a variety of C-C bond forming reactions,9,10 might
be ideal for effecting the condensation of aldehydes and
activated arenes. The preliminary results that illustrate the
efficiency and versatility of AuCl3-promoted condensation
to afford triaryl- and triheteroarylmethanes are described in
this letter.
In the first example, 2-methyl furan (1a) was treated with
benzaldehyde (2a) in the presence of AuCl3 (1 mol % based
on the aldehyde) in acetonitrile (Scheme 1).
triarylmethanes have been reported to exhibit antitumor and
antioxidant activities.6 Also, bisheteroarylmethanes are of
interest to the food industry as natural components of certain
food and beverage items as well as flavor agents in coffee.7
Although a number of methods are available for the synthesis
of triarylmethanes, most of them are multistep processes and/
or require harsh reaction conditions.8
In the quest to develop a mild and practical protocol for
the synthesis of triaryl-/triheteroarylmethanes, it was specu-
lated that gold(III), which has recently been shown to
After stirring the reaction mixture at room temperature
for 12 h, the bis(5-methylfur-2-yl)phenylmethane 3a was
(3) Greene, T. W.; Wuts, P. G. M. ProtectiVe Groups in Organic
Synthesis, 3rd ed.; Wiley: New York, 1999.
(9) For reviews, see: (a) Dyker, G. Angew. Chem. 2000, 112, 4407;
Angew. Chem., Int. Ed. 2000, 39, 4237. (b) Hashmi, A. S. K. Gold Bull.
2003, 36, 3. (c) Hashmi, A. S. K. Gold Bull. 2004, 37, 51. (d) Arcadi, A.;
Guiseppe, S. D. Curr. Org. Chem. 2004, 8, 795. (e) Hoffmann-Ro¨der, A.;
Krause, N. Org. Biomol. Chem. 2005, 3, 387.
(10) For selected examples, see: (a) Fukuda, Y.; Utimoto, K. J. Org.
Chem. 1991, 56, 3729. (b) Asao, N.; Takahashi, K.; Lee, S.; Kasahara, T.;
Yamamoto, Y. J. Am. Chem. Soc. 2002, 124, 12650. (c) Li, C.-J.; Yao, X.
J. Am. Chem. Soc. 2004, 126, 6884. (d) Yang, C. G.; He, C. J. Am. Chem.
Soc. 2005, 127, 6966. (e) Hashmi, A. S. K.; Schwarz, L.; Choe, J.-H.; Frost,
T. M. Angew. Chem., Int. Ed. 2000, 39, 2285. (f) Wei, C.; Li, C.-J. J. Am.
Chem. Soc. 2003, 125, 9584. (g) Shi, Z.; He, C. J. Am. Chem. Soc. 2004,
126, 5964. (h) Luo, Y.; Li, C.-J. Chem. Commun. 2004, 1930. (i) Reetz,
M. T.; Sommer, K. Eur. J. Org. Chem. 2003, 3485. (j) Reetz, M. T.;
Sommer, K. Gold-catalyzed Hydroarylation of Alkynes. In Handbook of
C-H Transformations, Vol.1 (Applications in Organic Synthesis); Dyker,
G., Ed.; Wiley-VCH: Weinheim, Germany, 2005, pp 157-166, 268-269.
(4) (a) Aldag, R. Photochromism based on dissociation processes. In
Photochromism: Molecules and Systems; Du¨rr, H., Bouas-Laurent, H., Eds.;
Elsevier: London, 1990. (b) Irie, M. J. Am. Chem. Soc. 1983, 105, 2078.
(5) (a) Rys, P.; Zollinger, H. Fundamentals of the Chemistry and
Application of Dyes; Wiley-Interscience: New York, 1972. (b) Muthyala,
R.; Katritzky, A. R.; Lan, X. Dyes Pigm. 1994, 25, 303.
(6) Mibu, N.; Sumoto, K. Chem. Pharm. Bull. 2000, 48, 1810.
(7) Katritzky, A. R.; Xie, L.; Fan, W.-Q. J. Org. Chem. 1993, 58, 4376.
(8) (a) Schick, J. W.; Crowley, D. J. J. Am. Chem. Soc. 1951, 73, 1377.
(b) Ungnade, H. E.; Crandall, E. W. J. Am. Chem. Soc. 1949, 71, 2209. (c)
Pratt, E. F.; Green, L. Q. J. Am. Chem. Soc. 1953, 75, 275. (d) Katritzky,
A. R.; Gupta, V.; Garot, C.; Stevens, C. V.; Gordeev, M. F. Heterocycles
1994, 38, 345. (e) Katritzky, A. R.; Toader, D. J. Org. Chem. 1997, 62,
4137. (f) Riad, A.; Mouloungui, Z.; Delmas, M.; Gaset, A. Synth. Commun.
1989, 19, 3169.
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Org. Lett., Vol. 7, No. 26, 2005

under the same conditions (Table 1). 2-Methyl thiophene
on reaction with benzaldehyde under the above con-
ditions yielded 35% of the adduct. The yield rose to
70% when the catalyst system was changed to 1 mol % of
AuCl3/3AgOTf.11 Various heterocyclic and aryl alde-
hydes as well as aliphatic aldehydes underwent the
reaction smoothly.
Table 1. Heteroarene Condensation Products with Yields
An electron-rich arene, 1,3,5-trimethoxybenzene, re-
quired the catalytic system AuCl3/3AgOTf and a slightly
elevated temperature (50 °C) to condense effectively with
benzaldehyde. However, with a more activated electrophile
(4-nitro benzaldehyde), the reaction took place at room
temperature to afford the tris adduct in good yield (Scheme
2).
With the perception that the reaction, if successful
with polyaldehydic compounds, would allow an unprec-
edented entry into the dendritic arena, a few exploratory
reactions were carried out. Thus, terephthalaldehyde was
reacted with indole and 2-methyl furan, and in both cases,
good yields of the condensation products were obtained
(Scheme 3).
The condensation of tris[(4-formyl)phenyl]amine with
heteroarenes yielded even more fascinating molecules (Scheme
4). Evidently, these products, in principle, can serve as core
structures for dendritic architectures.
In summary, it has been demonstrated that electron-
rich aromatic systems undergo an efficient condensation
reaction with various aldehydes under the influence of gold-
(III). It is reasonable to expect that the present work will
find much use in the synthesis of triaryl- and triheteroaryl-
methanes, which are very valuable compounds in many
respects.
Acknowledgment. Financial assistance from Council of
Scientific and Industrial Research (CSIR), Government of
India, is acknowledged.
Supporting Information Available: Experimental pro-
cedures and characterization data for all compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
a Isolated yield. b 1 mol % AuCl3/3AgOTf was used.
OL052423H
isolated in 93% yield. Other heterocycles such as indole,
1-methyl indole, and 3-methyl indole also reacted well
(11) A 1:3 mixture of AuCl3 and AgOTf acts as a better catalyst system,
though it is not clear what the active species is. See ref 10i for a discussion.
Org. Lett., Vol. 7, No. 26, 2005
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