Indole retrosynthetic analysis

For the retrosynthesis of indole (see Fig. 5.8), two routes (I/II) are proposed, as for pyrrole (see p 94). Route I suggests o-aminobenzyl ketone 1 or 6>-alkyl-A -acylaniline 2 as starting material on the basis of operations a - c. Their retroanalysis (d,e) in turn leads to 2-alkylaniline 5 and carboxylic acid derivative 6. Construction of the indole system should thus occur by N- or C-acylation of 5 (utilizing the o-nitrotoluene derivative 4) followed by cyclodehydration of 1/2. The alternative route n, based on retrosynthetic analysis g-i, leads to aniline via the a-(A -phenylamino)ketones 3 and to a-halo ketones 7 as possible precursors for the indole synthesis. 

Overman s retrosynthetic analysis is depicted in Scheme 1. Pentacyclic ketone 4, derived from allylic alcohol 7 by an aza-Cope-Mannich rearrangement of formaldiminium ion derivative 6 furnished 3 through the C5 hemiketal disconnection. An intramolecular oxidative coupling of a dienolate generated from indole-... 

The approach of Baran and coworkers features the fact that stephacidin A (126), which is a reduced monomer biogenetically related to stephacidin B (125), can be oxidized to avrainvillamide (127). The retrosynthetic analysis fundamentally differs from that of Myers in that the indole nucleus is already present in the starting material. Thus, one stereocenter is in the starting material and the other two stereocenters are installed simultaneously [54, 58] (Scheme 24). 

Scheme 4. Corey s retrosynthetic analysis of reverse prenylated indole 9.

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