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Synthesis 2013; 45(13): 1843-1852
DOI: 10.1055/s-0033-1338911
DOI: 10.1055/s-0033-1338911
paper
Further Investigations into the Regioselectivity of 6,7-Indole Aryne Cycloadditions with 2-Substituted Furans: Remarkable Contrasteric Preference Depends on Pyrrole and Benzene Ring Substitution
Further Information
Publication History
Received: 24 April 2013
Accepted after revision: 16 May 2013
Publication Date:
06 June 2013 (online)
This paper is warmly dedicated to Professor Scott Denmark on the occasion of his 60th birthday.
Abstract
A series of related 6,7-dibromoindole compounds were prepared to study the effects of pyrrole and benzene ring substitution patterns on the regioselectivity of 6,7-indole aryne cycloadditions with 2-tert-butylfuran. The arynes were generated by our metal–halogen exchange/elimination protocol. The results of this investigation reveal that substitution at the 3-position on the indole ring in particular results in remarkable regiocontrol that favored the contrasteric products. Aromatic conjugation at this site significantly enhanced this effect. However, the presence of most 4- or 5-substituents generally resulted in markedly reduced selectivity. Exceptions in this latter series included the 4-ethyl and 4-iodo cases both of which also gave predominantly contrasteric products even in the absence of a beneficial C-3 substituent.
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For reviews of arynes, see:
Bartoli indole synthesis:
Leimgruber–Batcho indole synthesis:
This conclusion is supported, for example, by the many different and creative strategies from various laboratories involved with the total synthesis of the family of trikentrins, some members of which feature a conjugated trans-butenyl appendage at C-5. See for example: