ORGANIC
LETTERS
2010
Vol. 12, No. 6
1364-1367
Selenium-Mediated Synthesis of Biaryls
through Rearrangement
Sohail A. Shahzad, Clotilde Vivant, and Thomas Wirth*
School of Chemistry, Cardiff UniVersity, Park Place, Cardiff CF10 3AT, U.K.
Received February 2, 2010
ABSTRACT
A new cyclization of ꢀ-keto ester substituted stilbene derivatives using selenium electrophiles in the presence of Lewis acids is described.
Substituted naphthols are obtained through cyclization and subsequent 1,2-rearrangement of aryl groups under very mild reaction conditions.
Selenium reagents have a very broad spectrum of applications
and are used as key reagents in organic synthesis.1 Usually
mild reaction conditions and high selectivities are associated
with selenium reagents. The formation of new carbon-carbon
bonds through electrophilic addition to double bonds is an
attractive strategy in organic synthesis. However, carbocy-
clizations mediated by selenium electrophiles have not been
investigated in much detail.2,3
cyclizations of malonate moieties onto alkenes.7 Herein we
use a similar approach for the synthesis of the stilbene
starting materials based on Mizoroki-Heck reactions, hy-
drolysis, and condensation steps. The palladium-catalyzed
cross-coupling reaction of methyl 2-iodobenzoate 1 with
different styrene derivatives afforded esters 2 in good yields,
and subsequent hydrolysis yielded the corresponding car-
boxylic acids 3 almost quantitatively (Scheme 1). Condensa-
tion of the carboxylic acid with potassium ethyl malonate
in the presence of triethylamine and magnesium dichloride
afforded the ꢀ-keto ester derivatives 4. NMR investigations
revealed that the stilbene ꢀ-keto esters 4 are in equilibrium
Polysubstituted naphthalenes are being used in many
areas such as pharmaceuticals, plant protection agents,
dyes, and many others.4 In addition, some natural products
with naphthalene or biaryl structures often exhibit biologi-
cal activities such as antimalarial properties and potent
anti-HIV activity or show potential for the treatment of
diabetes and cancer.5 Apart from their interesting biologi-
cal activity, biarylnaphthalene compounds also find ap-
plication as chiral reagents, ligands, and metal complexes
in synthesis.6
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Recently, we have reported the synthesis of dihydronaph-
thalene and benzofluorene derivatives by selenium-mediated
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2009, 1649.
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.
10.1021/ol100274e 2010 American Chemical Society
Published on Web 02/23/2010