Cascade reactions minfiensine

To demonstrate the power of these cascade sequences this methodology was successfully applied to total syntheses of several indole-derived alkaloids, for example, minfiensine [113]. By implementation of organocatalyzed cascade reactions the MacMillan group was able to dramatically reduce the number of reaction steps in total syntheses of strychnine, aspidospermidine, and kopsinine [114]. 

In 2010, the Padwa group reported a racemic synthesis of minfiensine (109) exploiting a cascade sequence involving a C—N union followed by an intramolecular Diels—Alder reaction (Scheme 13). 

Scheme 3.43 Enantioselective total synthesis of (+)-minfiensine via the key step reaction of organocatalytic Diels-Alder-cascade cyclization...

In the synthesis of (-l-)-Minfiensine by MaeMillan and coworkers, a novel Diels-Alder/amine cyclisation sequenee is aehieved using n with TBA (tri-bromoacetic acid) as the coeatalyst, allowing the synthesis of the complex tetracyclic pyrrolindoline core of the target molecule (87% yield, 96% ee), with low loadings possible (5 mol%). Similarly, MacMillan and coworkers have described the short nine-step synthesis of (—)-Vincorine, in which they employ the catalyst II and HBF4 as a cocatalyst for the formation of three stereocentres with the correet absolute and relative stereochemistry. The combination of an intermolecular Diels-Alder reaction with an iminium cyclisation cascade allowed formation of the tetracyclic alkaloid core in one step (70% yield, 95% ee). ... 

Minfiensine, a secoiridoid indole alkaloid, was isolated from the African plant Strychnos minfiensis by Massiot and co-workers in 1989. The unique structure feature of the 1,2,3,4-tetrahydro-9a,4a-(iminoethano)-9//-carbazole has received much attention for the synthetic efforts and has culminated in several elegant total syntheses. For example. Overman et al. reported on the first and second total synthesis of (-l-)-minfiensine. " In addition, Qin et al. revealed a synthesis of ( )-minfiensine in 2008. Recently, MacMillan and co-workers reported on a nine-step enantiose-lective total synthesis of (-l-)-minfiensine via the key step reaction of organocatalytic Diels-Alder cyclization and amine heterocyclization cascade (Scheme 21.32). For the key step reaction in their approach, reaction of 2-vinylindole 139 and 3 equivalents of propynal in the presence of secondary amine catalyst 140 followed by the addition of NaBH4, stereoselective afforded the tricyclic alcohol 142 via a iminium activated endo-selectiye Diels-Alder cycloaddition and a 5-exo amine heterocy cliz ation. 

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