Alkenyl halides, reaction with indole

The formation of disubstituted alkynes by coupling of terminal alkynes, followed by intramolecular attack of an alcohol or amine, is used for the preparation of benzofurans and indoles. The benzo[il)]furan 356 can be prepared easily by the reaction of o-iodophenol with a terminal alkyne[262]. The 2-substituted indole 358 is prepared by the coupling of 2-ethynylaniline (357) with aryl and alkenyl halides or triflates, followed by Pd(ll)-catalyzed cycliza-tion[263]. 

Pyrrole derivatives are prepared by the coupling and annulation of o-iodoa-nilines with internal alkynes[291]. The 4-amino-5-iodopyrimidine 428 reacts with the TMS-substituted propargyl alcohol 429 to form the heterocondensed pyrrole 430, and the TMS is removed[292]. Similarly, the tryptophane 434 is obtained by the reaction of o-iodoaniline (431) with the internal alkyne 432 and deprotection of the coupled product 433(293]. As an alternative method, the 2,3-disubstituted indole 436 is obtained directly by the coupling of the o-alky-nyltrifluoroacetanilide 435 with aryl and alkenyl halides or triflates(294]. 

Substituted 2-(morpholinocarbonyl)-6-(trifluoromethyl)furo[3,2-Z)]indole derivatives (341) have been obtained by the reaction of (340) with acyl chlorides, alkyl halides and alkenyl halides under basic conditions (Equation (7)) <86JMC2284>. 

Another heteroannulation is combination of aryl and alkenyl halides with ortho-functionalized phenylalkynes 95 to give heterocycles 97 such as benzofurans and indoles (Scheme 3.11). In this reaction, trans addition of Ar-Pd to a triple bond and endo cyclization, as shown by 96, occur. 

Subsequently, the same group reported a more practical method for preparing indoles by using the azaallylic anion as a synthon (Scheme 8) [36]. They found that imines 25 could couple with o-dihalobenzenes 26 to produce intermediates 27, which underwent an intramolecular aryl amination to afford 1,2,3-trisubstituted indoles 28. Because the azaallylic anion could be prepared by a Pd-catalyzed reaction of alkenyl halides and primary amines, they were able to develop a domino three-component synthesis of indoles. 

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