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. 2010 Mar 5;75(5):1652-8.
doi: 10.1021/jo902639f.

Iodine/palladium approaches to the synthesis of polyheterocyclic compounds

Saurabh Mehta  1 , Richard C Larock
Affiliations

Iodine/palladium approaches to the synthesis of polyheterocyclic compounds

Saurabh Mehta et al. J Org Chem. .

Abstract

A simple, straightforward strategy for the synthesis of polyheterocyclic compounds (PHCs) is reported, which involves iterative cycles of palladium-catalyzed Sonogashira coupling, followed by iodocyclization using I(2) or ICl. A variety of heterocyclic units, including benzofurans, benzothiophenes, indoles, and isocoumarins, can be efficiently incorporated under mild reaction conditions. In addition, variations of this strategy afford a variety of linked and fused PHCs.

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Figures

SCHEME 1
SCHEME 1. Iodocyclization Reaction
SCHEME 2
SCHEME 2. Generation of Polyheterocyclic Compounds by the General Strategya
Conditions: aAll Sonogashira reactions were carried out on a 0.25–5.0 mmol scale and the iodocyclization reactions were carried out on a 0.10–4.0 mmol scale using I2 or ICl (see the Supporting Information). bThis compound was prepared from 4c by desilylation.
SCHEME 3
SCHEME 3. Simultaneous and Stepwise Diiodination
SCHEME 4
SCHEME 4. Click Chemistry Followed by Iodo-desilylation
SCHEME 5
SCHEME 5. Double Sonogashira Coupling, Followed by Double Iodocyclization
SCHEME 6
SCHEME 6. Palladium-catalyzed Ullmann Reaction
SCHEME 7
SCHEME 7. Previously Reported Examples of 1,3-Diyne Cyclization
SCHEME 8
SCHEME 8. Preparation of 1,3-Diynes
SCHEME 9
SCHEME 9. Iodocyclization of Homo- and Hetero-1,3-diynes
SCHEME 10
SCHEME 10. Tuning of Reaction Conditions for Single or Double Cyclization
SCHEME 11
SCHEME 11. Elaboration of the Iodine-containing Products
SCHEME 12
SCHEME 12. Cyclocarbonylation Attempt
SCHEME 13
SCHEME 13. Alkyne Annulation Reaction Leading to a Fused PHC
See this image and copyright information in PMC

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