Indoles arene-alkynylated

After this work, the more challenging synthesis of arene-alkynylated indoles was investigated. Because of the enhanced reactivity of the pyrrole ring, the direct functionalization of indoles on the benzene ring is highly challenging. A domino process to access these compounds would therefore be very useful. They were able... 

Scheme 33 Domino cyclization-alkynylation for the synthesis of arene-alkynylated indoles...

Sonogashira reactions allow easy access to arenes with an alkynyl snbstitnent ortho to nitrogen, for example from ortho-iodo- and -bromo-nitrobenzenes, or ortho-iodo- and -bromo-A -acyl- (or N-sulfonyl)-arylamines, or even by conpUng acetylenes with 2-iodoaniUne itself.Conversion of orf/20-alkynyl-nitrobenzenes and -arylamines into indoles can be achieved in several ways, for example alkoxides add to the triple bond and form nitro-acetals, nitro-gronp rednction then acetal hydrolysis bringing ring closure. ... 

In this vein, alkynyl-functionalized (hetero)arenes were utilized in Pd-catalyzed arylation and cyclization events to reach tetrasubstituted alkenes. This strategy proved successful with an iV-phenylpropiolamide (Scheme 18a) [240] and N-(2-alkynylbenzyl)indoles (Scheme 18b) [241]. Copper catalysis was also viable, as demonstrated in reactions with 2-ethynyl anilides to yield benzoxazines (Scheme 18c) [242]. A copper-catalyzed carboarylation of electron-rich alkynes... 

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