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Synlett 2011(18): 2599-2604  
DOI: 10.1055/s-0031-1289561
SYNPACTS
© Georg Thieme Verlag Stuttgart ˙ New York

Understanding and Modulating Indolyne Regioselectivities

Sarah M. Bronner, Adam E. Goetz, Neil K. Garg*
Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Dr. East, Los Angeles, CA 90095, USA
Fax: +1(310)206-1843; e-Mail: neilgarg@chem.ucla.edu;
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Publication History

Received 13 July 2011
Publication Date:
25 October 2011 (online)

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Abstract

Heterocyclic arynes hold much promise for applications in modern synthetic chemistry. One particular class of hetarynes is those derived from the indole heterocycle (i.e., indolynes). Indolynes can be generated under mild fluoride-based reaction conditions using silyltriflate precursors. Indolyne-trapping experiments provide access to benzenoid-substituted indoles in a controlled manner with synthetically useful yields. Regioselectivities can be predicted prior to experiments using simple calculations, ultimately allowing for the modulation of selectivities by careful design. This strategy has enabled a concise synthesis of indolactam V.

Key words

arynes - indoles - regioselectivity - total synthesis - indolynes

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21

A Reaxys search reveals that over 100,000 bioactive indole-containing compounds have been discovered. See ref. 31.

28

The B3LYP/6-31G(d) geometry-optimization studies of indolynes could also be carried out using MacSpartan, computations for simple hetarynes are typically complete within 10 min.

31

Reaxys, version 1.0.8822; Elsevier Properties SA: Frankfurt, 2011.