Electronic Nature of Ketone Directing Group as a Key To Control C‑2 vs C‑4 Alkenylation of Indoles

A novel mode of achieving site selectivity between C-2 and C-4 positions in the indole framework by altering the property of the ketone directing group is disclosed. Methyl ketone, as directing group, furnishes exclusively C-2 alkenylated product, whereas trifluoromethyl ketone changes the selectivi...

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Bibliographic Details
Published in:Organic letters 2016-11, Vol.18 (21), p.5496-5499
Main Authors: Lanke, Veeranjaneyulu, Bettadapur, Kiran R, Prabhu, Kandikere Ramaiah
Format: Article
Language:English
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Summary:A novel mode of achieving site selectivity between C-2 and C-4 positions in the indole framework by altering the property of the ketone directing group is disclosed. Methyl ketone, as directing group, furnishes exclusively C-2 alkenylated product, whereas trifluoromethyl ketone changes the selectivity to C-4, indicating that the electronic nature of the directing group controls the unusual choice between a 5-membered and a 6-membered metallacycle. The screening of other carbonyl-derived directing groups reveals that strong and weak directing groups exhibit opposite selectivity. Experimental controls and deuteration experiments lend support to the proposed mechanism.
ISSN:1523-7060
1523-7052
DOI:10.1021/acs.orglett.6b02698