Cyclopentadienones as intermediates for the synthesis of highly functionalized biaryls

Article abstract of DOI:10.1016/j.tetlet.2003.08.123

A new approach to the synthesis of substituted biaryls, via Diels-Alder reaction between cyclopentadienones and arylacetylenes, is described.

Full text of DOI:10.1016/j.tetlet.2003.08.123

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 8525–8527
Cyclopentadienones as intermediates for the synthesis of highly
ꢀ
functionalized biaryls
Anthony J. Pearson* and Jin Bum Kim
Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA
Received 23 July 2003; revised 27 August 2003; accepted 27 August 2003
Abstract—A new approach to the synthesis of substituted biaryls, via Diels–Alder reaction between cyclopentadienones and
arylacetylenes, is described.
©
2003 Elsevier Ltd. All rights reserved.
1
. Introduction
dienones that are versatile intermediates for organic
synthesis, because the silicon tether can be removed
under conditions that are non-invasive toward the reac-
tive cyclopentadienone. The symmetrically substituted
compound 1 was chosen as a substrate for the present
study in order to circumnavigate regiochemical issues in
the synthesis of the target biaryl structures.
Biaryls are important subunits in a broad range of
natural product molecules, as well as ligands used in
asymmetric catalysis,
Numerous methods have been developed for the con-
struction of these molecules, mostly by direct coupling
1
2,3
3
and materials structures.
1
,4
of two suitably activated aromatic moieties. Nonethe-
less, alternative approaches to these structures that
allow introduction of dense functionality, as well as the
potential for generating chiral biaryl structures, repre-
sent useful additions to the currently available method-
ology. One such approach might be the reaction of a
cyclopentadienone derivative with a suitably functional-
2
. Results and discussion
In order to ensure that 1 is a suitable substrate for
Diels–Alder reaction/CO extrusion to afford aromatic
molecules, we examined its reaction with dimethyl
acetylenedicarboxylate, which proceeded smoothly in
toluene at 110°C to afford the hexasubstituted benzene
derivative 2. It should be mentioned that, since we have
access to a wide range of cyclopentadienone structures
using the aforementioned cyclocoupling methodology,
this procedure could in principle afford numerous hexa-
substituted aromatic compounds. Moreover, the known
5
ized alkyne, which is known to generate aromatic
molecules by a Diels–Alder cycloaddition followed by
cheletropic extrusion of carbon monoxide. While this
reaction has been reported for alkynes such as dimethyl
acetylenedicarboxylate, as far as we are aware there
have been no reports of its application to biaryl synthe-
sis, wherein an arylalkyne is used as the dienophile.
This paper reports our initial investigations into this
reaction, which appears to provide a potentially useful
alternative approach to biaryl synthesis.
7
chemistry of arylsilanes, such as ipso electrophilic sub-
stitution, is expected to generate a rich chemistry for
these products.
We recently reported a method for preparing unsym-
metrically substituted cyclopentadienones by a silicon
tethered [2+2+1] cyclocarbonylation reaction of two
6
alkynes promoted by pentacarbonyliron. This reaction
has the potential to afford a broad range of cyclopenta-
Our first attempt to utilize 1 as a precursor to biaryls
examined its reaction with the simple methyl phenyl-
propiolate (3), a known compound that was prepared
by esterification of the corresponding acid. No reaction
Keywords: biaryl; cyclopentadienone; alkyne; cycloaddition.
Supplementary data associated with this article can be found at
doi:10.1016/j.tetlet.2003.08.123
ꢀ
*
0
Corresponding author.
040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.08.123

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A. J. Pearson, J. B. Kim / Tetrahedron Letters 44 (2003) 8525–8527
was observed in toluene at 110°C, or in mesitylene at
40°C, but higher temperature (decalin, 210°C, 8 h)
Reaction of 1 with 12a and 12b afforded similar yields
of biaryl products 13 and 14 as observed for the
unsubstituted phenylpropiolonitrile, indicating that the
presence of an electron withdrawing group on the aro-
matic ring does not have a significant effect on the
electronic nature of the dienophile, and that the pres-
ence of one ortho substituent does not lead to signifi-
cant steric retardation of the cycloaddition reaction.
1
promoted the formation of biaryl 4, in low yield (25%).
Owing to its less electron deficient nature, alkyne 3 is a
less effective dienophile than dimethyl acetylenedicar-
boxylate, and we therefore investigated activating
groups other than ester in an effort to generate biaryls
in good yield under somewhat milder reaction condi-
8
9
tions. Compounds 5 and 6 were prepared by pub-
lished procedures and subjected to Diels–Alder reaction
with 1: 5 in mesitylene for 8 h at 140°C afforded biaryl
7
in 40% yield, while 6 under identical conditions
3. Conclusions
produced 8 in 75% yield.
In summary, we have demonstrated that cyclopenta-
dienones are potentially useful intermediates for the
construction of multi-substituted biaryl structures.
Clearly there is much to be done in further develop-
ment of this protocol, which will form the basis for
future studies in our laboratory.
Of greater interest is the construction of biaryls con-
taining substituents on both aromatic rings, especially
at the o and o% positions, for which purpose the reac-
tion between 1 and substituted phenylacetylenes was
studied. Two dienophiles, 12a and 12b, were prepared
via the Sonagashira procedure reported by Thorand
1
0
and Krause to access the intermediates 10a and 10b.
The TMS group was removed from each intermediate
1
1
by stirring with K CO in methanol, and the resulting
4. Supplementary material
2
3
arylacetylenes were converted to the nitriles using the
electrophilic cyanation method described by Wu et al.
Spectroscopic characterization data for all new com-
pounds, and copies of their H and C NMR spectra.
1
2
1
13
(
Scheme 1).
Scheme 1.

A. J. Pearson, J. B. Kim / Tetrahedron Letters 44 (2003) 8525–8527
8527
Acknowledgements
Suzuki, A. Pure Appl. Chem. 1985, 57, 1749; Suzuki, A.
Pure Appl. Chem. 1994, 66, 213; Stille, J. K. Angew.
Chem., Int. Ed. Engl. 1986, 25, 508; Miyara, N.; Suzuki,
A. Chem. Rev. 1995, 95, 2457.
. (a) Allen, C. F. H.; Ryan, R. W., Jr.; VanAllan, J. A. J.
Org. Chem. 1962, 27, 778; (b) Knolker, H. J.; Baum, E.;
Heber, J. Tetrahedron Lett. 1995, 36, 7647; (c) Harano,
K.; Yasuda, M.; Kanematsu, K. J. Org. Chem. 1982, 47,
4736 and references cited therein; (d) Jikyo, T.; Eto, M.;
Harano, K. J. Chem. Soc., Perkin Trans. 1 1998, 3463; (e)
Jikyo, T.; Eto, M.; Harano, K. Tetrahedron 1999, 55,
6051.
6. Pearson, A. J.; Kim, J. B. Org. Lett. 2002, 4, 2837.
7. Fleming, I. In Comprehensive Organic Chemistry Jones,
D. N., Ed.; Pergamon Press: Oxford, 1979; Vol. 3, Chap-
ter 13.
8. Luo, F.-T.; Wang, R.-T. Tetrahedron Lett. 1993, 34,
5911.
We are grateful to the National Science Foundation for
financial support of this research (CHE-0131043).
5
References
1
2
. For a recent review of biaryl synthesis as well as an
overview of natural product structures based on biaryls,
see: Lloyd-Williams, P.; Giralt, E. Chem. Soc. Rev. 2001,
3
0, 145.
. Examples include the binaphthyl-derived ligands such as
BINOL: Mikami, K.; Motoyama, Y. In Encyclopedia of
Reagents for Organic Synthesis, Paquette, L. A., Ed.;
John Wiley and Sons: Chichester, 1995; Vol. 1, p. 403;
Guiry, P. J.; McCarthy, M.; Lacey, P. M.; Saunders, C.
P.; Kelly, S.; Connolly, D. J. Curr. Org. Chem. 2000, 4,
8
21.
9. Truce, W.; Wolf, G. C. J. Org. Chem. 1971, 36, 1727.
10. Thorand, S.; Krause, N. J. Org. Chem. 1988, 63, 8551.
11. Hirsh, K. A.; Wilson, S. R.; Moore, J. S. J. Am. Chem.
Soc. 1997, 119, 10401.
3
4
. Pu, L. Chem. Rev. 1998, 98, 2405.
. Recent reviews: Bringmann, G.; Tasler, S. Tetrahedron
2
001, 57, 331; Hassan, J.; Sevignon, M.; Gozzi, C.;
Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359;
Amatore, C.; Jutand, A. Acc. Chem. Res. 2000, 33, 314;
12. Wu, Y.-Q.; Limburg, D. C.; Wilkinson, D. E.; Hamilton,
G. S. Org. Lett. 2000, 2, 795.