Syn th esis of 3-Su bstitu ted 4-Ar oylisoqu in olin es via P d -Ca ta lyzed
Ca r bon yla tive Cycliza tion of 2-(1-Alk yn yl)ben za ld im in es
Guangxiu Dai and Richard C. Larock*
Department of Chemistry, Iowa State University, Ames, Iowa 50011
larock@iastate.edu
Received J une 5, 2002
A number of 3-substituted 4-aroylisoquinolines have been prepared in good yields by treating N-tert-
butyl-2-(1-alkynyl)benzaldimines with aryl halides in the presence of CO and a palladium catalyst.
Synthetically the methodology provides a simple and convenient route to isoquinolines containing
an aryl, alkyl, or vinylic group at C-3 and an aroyl group at C-4 of the isoquinoline ring. The reaction
is believed to proceed via cyclization of the alkyne containing a proximate nucleophilic center
promoted by an acylpalladium complex.
SCHEME 1
In tr od u ction
Alkyne-based palladium-catalyzed reactions provide
some of the most versatile and efficient routes to hetero-
cyclic derivatives (Scheme 1).1 A variety of heterocycles
have been prepared through in situ hydroarylation
(hydrovinylation)/cyclization reactions,2 in situ coupling/
cyclization reactions,3 and annulation reactions promoted
by σ-vinyl- and σ-arylpalladium complexes.1,4 Hetero-
cyclization promoted by σ-vinyl- and σ-arylpalladium
complexes is extremely valuable, since generation of
the heterocyclic skeleton accommodates functionalities
amenable to further functional group manipulation and
affords a rapid increase in molecular complexity. When
such reactions are carried out in the presence of carbon
monoxide, one carbon-heteroatom bond and two carbon-
carbon bonds are generated in a single synthetic opera-
tion.
bond has been employed in the synthesis of ketone-
containing indoles5 and benzo[b]furans, we thought that
analogous chemistry might be used to generate the
isoquinoline skeleton. We have recently reported conven-
ient methods for the preparation of 3-monosubstituted6
and 3,4-disubstituted isoquinolines,7 disubstituted â- and
γ-carbolines,8 and monosubstituted â- and γ-carbolines9
by the palladium-promoted cyclization of alkynylimines.
Herein we report analogous acylpalladation chemistry of
Since the acylpalladation of alkynes containing oxygen
and nitrogen nucleophiles near the carbon-carbon triple
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10.1021/jo026016k CCC: $22.00 © 2002 American Chemical Society
Published on Web 09/12/2002
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J . Org. Chem. 2002, 67, 7042-7047