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1.2.3.4.2 Intramolecular Addition of Nitrogen Nucleophiles Followed by Allylation

DOI: 10.1055/sos-SD-001-00206

Takacs, J. M.; Vayalakkada, S.; Jiang, X.Science of Synthesis, (20011291.

2-Substituted 3-allyl-1H-indoles 125 are synthesized by the palladium-catalyzed cyclizationallylation of o-alkynylanilines 114 with allylic chlorides 122 (Scheme 32).[‌26‌] Treatment of a mixture of 114 and allyl chloride with bis(acetonitrile)dichloropalladium (5mol%) in acetonitrile gives the non-allylated product, the 2-substituted 1H-indole 115. As it is proposed that 115 arises via protonolysis of the vinylpalladium(II) intermediate 123, various bases have been added to the reaction mixture. The addition of potassium acetate or proton sponge does not improve the allylation, but the addition of 2-methyloxirane (124) is quite successful. For example (Table 2, entry 3), treatment of 2-(hex-1-ynyl)-N-(methoxycarbonyl)aniline (114, R1=Bu; R2=CO2Me) and allyl chloride (10 equiv) with 5mol% bis(acetonitrile)dichloropalladium and 2-methyloxirane (10 equiv) in acetonitrile (rt, 20h) gives 125 (R1=Bu; R2=CO2Me; R3=R4=R5=H) in 73% yield with only 5% of 115 (R1=Bu; R2=CO2Me). In general, N-acylated o-alkynylanilines are better substrates than the primary aniline.

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