2- alkynylanilines intramolecular cyclization

Indole synthesis.9 A new route to 2-substituted indoles is based on the Pd(0) coupling of alkynylstannanes with 2-bromoanilines or 2-trifloxyanilines to give 2-alkynylanilines. Intramolecular cyclization of these products with a variety of Pd(II) catalysts provides substituted indoles. 

Palladium-catalyzed intramolecular cyclization of the imine 84, which is available from the corresponding o-alkyny-laniline and thiophene-2-carboxaldehyde, affords the indole 85 (Scheme 55). Several other related indoles have been prepared in this manner by varying the aldehyde or 0-alkynylaniline components <2000JA5662, CHEC-III (3.03.3)288>. 

The cyclization of 2-alkynylaniline derivatives has become a general method for the assembly of 2-substituted indoles [2, 4]. While a range of other transition metals and Lewis acids can mediate similar intramolecular cyclizations, a useful feature of palladium catalysis is that it can also be employed to assemble the cyclization precursors. The latter is often accomplished by coupling more traditional palladium-catalyzed coupling chemistry with cyclization, and provides an avenue to readily expand the diversity of indole products available. As illustrated with the examples in Scheme 6.5, this can be done via the Sonogashira coupling of 2 with R-X [5], the Stille... 

Sakai and Konakahara et al. found that InBrs is effective in catalyzing the intramolecular cyclization of 2-alkynylanilines to form polysubstituted indoles [232] (Figure 8.109). Activation of the alkyne by InBrs, increasing the electrophilicity of the triple bond, is the role played by InBrs in this case. The authors also reported in the same paper the synthesis of idolyl amine derivatives by utilizing the indole generated in situ to add to imines in the presence of TMSCl with increased catalyst use. 

A general and convenient route to 2-substituted benzofurans or indoles is based on intramolecular annulation of 2-alkynylphenols or 2-alkynylanilines (Scheme 23), which are in turn readily available via alkynylaryl cross-coupling reactions. In a representative example, base-induced cyclization of the precursors 37 with concomitant elimination of the TMS-moiety affords the indoles 38 in good yields (Scheme 24) <1997JOC6507>. 

Later, Arcadi showed that /J-keto-imines react with alkynes intramolecularly to give pyrroles. The intermolecular animation with aniliaes was later developed by Hayashi and Tanaka using a cationic Au(I) catalyst to form imines (equation 27). More recently, Arcadi etal. developed an intramolecular version for the cyclization of o-alkynylanilines to form indoles (equation 28) and Li reported a double intra- and intermolecular hydroamination to obtain A-vinylindoles. " O-Substituted hydroxylamines can also undergo this type of transformation to dihydroisoxazole derivatives. " " Tandem sequences that involve a first alkyne-hydroamination step with anilines have been recently developed " " and are similar to the previonsly discnssed additions with phenols that access isoflavone skeletons. 

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