Competition Studies in Alkyne Electrophilic Cyclization Reactions
Saurabh Mehta, Jesse P. Waldo, and Richard C. Larock*
Department of Chemistry, Iowa State UniVersity, Ames, Iowa 50011
ReceiVed October 1, 2008
The relative reactivity of various functional groups toward alkyne electrophilic cyclization reactions has
been studied. The required diarylalkynes have been prepared by consecutive Sonogashira reactions of
appropriately substituted aryl halides and competitive cyclizations have been performed using I2, ICl,
NBS and PhSeCl as electrophiles. The results indicate that the nucleophilicity of the competing functional
groups, polarization of the alkyne triple bond, and the cationic nature of the intermediate are the most
important factors in determining the outcome of these reactions.
SCHEME 1. Electrophilic Cyclization
Introduction
Alkynes are versatile building blocks in organic synthesis.
A wide range of carbocycles and heterocycles have been
prepared by the electrophilic cyclization of functionally sub-
stituted alkynes1 and by transition metal-catalyzed annulations.2
Recently, we and others have reported that the electrophilic
cyclization of alkynes using halogen, sulfur and selenium
electrophiles can be a very powerful tool for the preparation of
a wide variety of interesting carbocyclic and heterocyclic
compounds (Scheme 1), including benzofurans,3 furans,4 ben-
zothiophenes,5 thiophenes,6 benzopyrans,7 benzoselenophenes,8
selenophenes,9 naphthols,10 indoles,11 quinolines,12 isoquino-
lines,13 R-pyrones,14 isocoumarins,14 isochromenes,15 isoindoli-
nones,16 naphthalenes17 and polycyclic aromatics,18 isoxazoles,19
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10.1021/jo802196r CCC: $40.75
Published on Web 12/23/2008
2009 American Chemical Society
J. Org. Chem. 2009, 74, 1141–1147 1141