Kraus indole synthesis

Kraus and his group extended their Wittig-Madelung indole synthesis to other activated benzylic systems as shown in Scheme 6 (equations 1-3) [17]. These include phenylsulfonyl, thiomethyl, and cyano, and this team applied this chemistry to a synthesis of the alkaloid isocryp-tolepine. As we saw twice in the previous chapter, the cycli-zation of phosphonium salt 15 affords quinolone 16, which was used to synthesize both neocryptolepine (17) and isocryptolepine (18). 

An important variation of the Jones-Schmid indole synthesis is the base-mediated cyclization onto esters, which affords 3-hydroxyindoles (indoxyl tautomers) under mild conditions. Three case studies are shown in Scheme 2 (equations 1-3) [18-20]. This chemistry, like that in Table 1 (Entries 4-11), represents a powerful route to C-3 functionalized indoles. Kraus and coworkers use the steri-cally hindered phosphazine base, P -t-Bu, to prepare the 5,6-dihydroindolo[2,l-a]isoquinoline ring system (equation 4) [21]. Several derivatives display immunosuppressive activity. 

Kraus has reported the synthesis of a tricyclic indole related to the pyrroloiitdnoquinone marine naniral products fScheme 10 9, in which an intramolecnlar S jAr and the reducdve cyclizadon of anitro aldehyde are involved as key steps Related target compounds have been prepared by Jonle and coworkers via a sirrular strategy... 

On the other hand, the synthesis of the makaluvamine family by route b shown in Schemes 2 and 4 has rarely been reported. Kraus et al. reported the total S3mthesis of makaluvamine C (Scheme 7). In their synthesis, the 6,6-bicyclic compound 14 was formed first. The reduction of 14 then gave the indole 15, which was converted to makaluvamine C by demethylation and in situ oxidation with Fremy s salt [49]. 

Kraus et al. described a total synthesis of makaluvamine C that proceeds through initial formation of quinoline ring followed by formation of the indole moiety and Fremy s salt promoted oxidation of the 4-methoxyaniline group (Scheme 9.3) [36]. In this approach, the 6,6-bicyclic compound 6 was formed first. 

---