Indoles polyfunctionalized, 3-

Metalation of the amidine 87, followed by introduction of 2-methoxyallyl bromide, furnished the intermediate 88, which underwent acid-induced cyclization to the product 89 (Scheme 12), illustrating an interesting approach to polyfunctionalized indoles suitable for further elaboration <20020L1819>. 

Enders et al. [75] developed a synthesis of polyfunctionalized 3-(cyclohex-enylmethyl)-indoles 125 via a quadruple domino Friedel-Crafts-type Michael-Michael-aldol condensation reaction, in 2010. This cascade sequence is initiated by a Friedel-Crafts reaction of indole (126) by an iminium activation mode to the enal, followed sequentially by an enamine- and an iminium-mediated Michael addition. After an intramolecular aldol-condensation, four C-C bonds are formed and the domino product is constructed bearing three contiguous stereogenic centers (Scheme 10.34). 

Regarding the 2-chloroanilines, a general palladium-catalyzed procedure was reported in 2004 by Nazare and co-workers. ° The procedure represents a very efficient method for the synthesis of polyfunctionalized indoles by direct reaction of substituted 2-chloroanilines with cyclic or acyclic ketones (Scheme 2.116). The procedure is simple to carry out and broadly applicable all the desired products were isolated in good yields. 

Relying, as in the previous studies, on the capability of secondary amine catalysts to activate both nucleophile and electrophile, Enders assembled a quadruple domino Friedel-Crafts-type/Michael/Michael/aldol condensation sequence, affording an efficient and direct asymmetric synthesis of polyfunctionalized 3-(cyclohexenylmethyl)-indoles 172 with moderate to high yields (Scheme 2.55) [82]. 

D. Enders, C. Wang, M. Mukanova, A. Greb, Chem. Commun. 2010, 46, 2447-2449. Organocatalytic asymmetric synthesis of polyfunctionalized 3-(cyclohexenyhnethyl)-indoles via a quadruple domino Friedel-Crafts-type/Michael/Michaehaldol condensation reaction. 

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