Fischer indolization of octahydroindol-6-one derivatives revisited: diastereoisomerization and racemization processes

Fischer indolization of enantiopure 2-methoxycarbonyl-cis-octahydroindol-6-ones using AcOH as a catalyst induces racemization of the octahydropyrrolocarbazoles obtained. Conversely, when using TsOH, the α-amino ester moiety preserves its configuration, although the other stereogenic centers show a partial or total stereolability according to the constitutional framework.

Figure optionsDownload as PowerPoint slide

(2S,3aS,10aR)-1-Benzyl-2-methoxycarbonyl-1,2,3,3a,4,9,10,10a-octahydropyrrolo[2,3-b]carbazoleC23H24N2O2[α]D22=-102 (c 1.25, CHCl3)Source of chirality: l-tyrosineAbsolute configuration: (2S,3aS,10aR)

(2S,3aR,10aR)-1-Benzyl-2-methoxycarbonyl-1,2,3,3a,4,9,10,10a-octahydropyrrolo[2,3-b]carbazoleC23H24N2O2[α]D22=-129 (c 2.14, CHCl3)Source of chirality: l-tyrosineAbsolute configuration: (2S,3aR,10aR)

(2S,3aS,10aS)-1-Benzyl-2-methoxycarbonyl-1,2,3,3a,4,9,10,10a-octahydropyrrolo[2,3-b]carbazoleC23H24N2O2[α]D22=3 (c 0.5, CHCl3)Source of chirality: l-tyrosineAbsolute configuration: (2S,3aS,10aS)

(2S,3aS,10cR)-1-Benzyl-2-methoxycarbonyl-1,2,3,3a,4,5,6,10c-octahydropyrrolo[3,2-c]carbazoleC23H24N2O2[α]D22=-13 (c 1.4, CHCl3)Source of chirality: l-tyrosineAbsolute configuration: (2S,3aS,10cR)