ORGANIC
LETTERS
2007
Vol. 9, No. 26
5589-5592
Biaryl Synthesis via Palladium-Catalyzed
Aryne Multicomponent Coupling
Jaclyn L. Henderson,† Andrew S. Edwards,‡ and Michael F. Greaney*,†
UniVersity of Edinburgh, School of Chemistry, Joseph Black Building, King’s
Buildings, West Mains Road, Edinburgh EH9 3JJ, U.K., and Organon Laboratories
Ltd., Newhouse, Lanarkshire ML1 5SH, U.K.
Received October 26, 2007
ABSTRACT
Aryl iodides have been introduced as electrophiles in the three-component Heck coupling of arynes. Following optimization studies to favor
three- versus two-component coupling, the reaction proceeds in good yield to afford a variety of functionalized biaryls.
The biaryl motif occupies an iconic role in chemistry, being
a key structural feature of natural products, novel optical
and mechanical materials, drugs, agrochemicals, and other
biologically active molecules. The assembly of functionalized
biaryls using transition-metal-catalyzed tandem reactions,
whereby multiple carbon-carbon or carbon-heteroatom
bonds are formed in a single step, is a highly attractive
approach to these valuable compounds that has widespread
application.1 The incorporation of arynes into such multi-
component coupling processes offers a unique entry point
into functionalized aromatics and is a rapidly growing area
of research.2 Pioneering work from the Pere´z/Guitia´n and
Yamamoto groups used π-allyl palladium complexes, alkynes,
and arynes to synthesize naphthalenes and phenanthrenes,3,4
setting the stage for a series of developments in transition-
metal-catalyzed aryne multicomponent couplings.5-11 Until
recently, a limitation of such aryne multicomponent coupling
processes was the requirement for allyl halides as the
electrophilic component. Work from our own laboratory
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V.; Yamamoto, Y. J. Am. Chem. Soc. 2000, 122, 7280-7286.
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† University of Edinburgh.
‡ Organon Laboratories.
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Synthesis 2006, 4093-4112. (b) Guitia´n, E.; Pe´rez, D.; Pen˜a, D. Top.
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10.1021/ol702584t CCC: $37.00
© 2007 American Chemical Society
Published on Web 11/22/2007