Document Detail


Direct palladium-catalyzed C-2 and C-3 arylation of indoles: a mechanistic rationale for regioselectivity.
MedLine Citation:
PMID:  15926829     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have recently developed palladium-catalyzed methods for direct arylation of indoles (and other azoles) wherein high C-2 selectivity was observed for both free (NH)-indole and (NR)-indole. To provide a rationale for the observed selectivity ("nonelectrophilic" regioselectivity), mechanistic studies were conducted, using the phenylation of 1-methylindole as a model system. The reaction order was determined for iodobenzene (zero order), indole (first order), and the catalyst (first order). These kinetic studies, together with the Hammett plot, provided a strong support for the electrophilic palladation pathway. In addition, the kinetic isotope effect (KIE(H/D)) was determined for both C-2 and C-3 positions. A surprisingly large value of 1.6 was found for the C-3 position where the substitution does not occur (secondary KIE), while a smaller value of 1.2 was found at C-2 (apparent primary KIE). On the basis of these findings, a mechanistic interpretation is presented that features an electrophilic palladation of indole, accompanied by a 1,2-migration of an intermediate palladium species. This paradigm was used to design new catalytic conditions for the C-3 arylation of indole. In case of free (NH)-indole, regioselectivity of the arylation reaction (C-2 versus C-3) was achieved by the choice of magnesium base.
Authors:
Benjamin S Lane; Meghann A Brown; Dalibor Sames
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  127     ISSN:  0002-7863     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-06-01     Completed Date:  2005-07-28     Revised Date:  2007-01-29    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8050-7     Citation Subset:  IM    
Affiliation:
Department of Chemistry, Columbia University, 3000 Broadway, New York, New York 10027, USA.
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MeSH Terms
Descriptor/Qualifier:
Benzene Derivatives / chemical synthesis,  chemistry
Catalysis
Deuterium Exchange Measurement
Indoles / chemical synthesis,  chemistry*
Kinetics
Palladium / chemistry
Substrate Specificity
Chemical
Reg. No./Substance:
0/Benzene Derivatives; 0/Indoles; 603-76-9/1-methylindole; 7440-05-3/Palladium
Comments/Corrections
Erratum In:
J Am Chem Soc. 2007 Jan 10;129(1):241

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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