ORGANIC
LETTERS
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Vol. XX, No. XX
000–000
Straightforward Synthesis of
Dihydrobenzofurans and Benzofurans
from Arynes
Eito Yoshioka, Hidekazu Tanaka, Shigeru Kohtani, and Hideto Miyabe*
School of Pharmacy, Hyogo University of Health Sciences, Minatojima, Chuo-ku,
Kobe 650-8530, Japan
Received June 17, 2013
ABSTRACT
Synthesis of dihydrobenzofurans was achieved by a route involving the insertion of arynes into formamides followed by trapping with zinc
enolates of R-chlorinated methines. Benzofurans were generated from dihydrobenzofurans having a ketone group via the addition of an ethyl
anion, the retro-aldol type reaction, and the elimination of an amino group.
2,3-Dihydrobenzofurans and benzofurans are useful
building blocks as well as core structures in biologically
active natural products.1 Most of the reported synthetic
approaches have involved the use of the oxygen-atom-
containing arenes such as ortho-functionalized phenols or
other phenol derivatives.2 Few methods are based on the
aromatic CꢀO bond formation;3 thus, we felt attracted to
the possibility of a new aromatic CꢀO bond-forming route
starting from arynes.
In recent years, aryne chemistry has made great advances
in synthetic chemistry.4,5 We have developed the effi-
cient insertion of arynes, in situ generated from ortho-
(trimethylsilyl)aryl triflates6 and the fluoride ion, into the
CdO π-bond of formamides (Figure 1).7,8
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10.1021/ol4017063
XXXX American Chemical Society