Pentacyclic pyrrolo[3,4-a]carbazole-1,3(2H)-diones are accessed via two key synthetic steps, an intermolecular Diels–Alder (D–A) reaction between an N-protected 3-vinyl-1H-indole and N-methyl-maleimide, and a Lewis acid-catalysed intramolecular carbonyl-ene cyclisation reaction. Cyclopentyl- or cyclohexyl-containing scaffolds can be formed through variation in the length of the alkyl tether, whilst the observed stereospecificity of carbonyl-ene cyclisation supports a concerted mechanism.

Functionalised tetrahydrocarbazoles are accessed through an enantioselective organocatalysed Diels–Alder reaction of 3-vinyl-1H-indole with a suitable dienophile in combination with an in situ N-protection. A subsequent diastereospecific ene reaction is then used to transfer chirality from the 10a to the 5 position with rearomatisation of the indolic ring, to give the target tetrahydrocarbazoles with high % ee. The in situ introduction of different N-protecting groups is explored along with their influence on the subsequent ene reactions.(3aS,10aS,10bS)-2-methyl-10-tosyl-4,10,10a,10b-tetrahydropyrrolo[3,4-a]carbazole-1,3(2H,3aH)-dioneC22H20N2O4SEe = >95% from HPLC[α]D25 = +180 (c 0.16, CHCl3)Source of chirality: 1-(3,5-bis(trifluoromethyl)phenyl)-3-((S)-(6-methoxyquinolin-4-yl)((1S,2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)thiourea(3aS,5S,10bS)-5-(hydroxy(phenyl)amino)-2-methyl-10-tosyl-4,5,10,10b-tetrahydropyrrolo[3,4-a]carbazole-1,3(2H,3aH)-dioneC28H25N3O5SEe = >95% from HPLC[α]D25 = +42 (c 0.5, CHCl3)Source of chirality: 1-(3,5-bis(trifluoromethyl)phenyl)-3-((S)-(6-methoxyquinolin-4-yl)((1S,2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)thiourea(3aS,5S,10bS)-5-(hydroxy(o-tolyl)amino)-2-methyl-10-tosyl-4,5,10,10b-tetrahydropyrrolo[3,4-a]carbazole-1,3(2H,3aH)-dioneC29H27N3O5SEe = >95% from HPLC[α]D25 = +44 (c 0.5, CHCl3)Source of chirality: 1-(3,5-bis(trifluoromethyl)phenyl)-3-((S)-(6-methoxyquinolin-4-yl)((1S,2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)thiourea(3aS,5S,10bS)-5-((S)-hydroxy(perfluorophenyl)methyl)-2-methyl-10-tosyl-4,5,10,10b-tetrahydropyrrolo[3,4-a] carbazole-1,3(2H,3aH)-dioneC29H21F5N2O5SEe = >95% from HPLC[α]D25 = +56 (c 0.6, CHCl3)Source of chirality: 1-(3,5-bis(trifluoromethyl)phenyl)-3-((S)-(6-methoxyquinolin-4-yl)((1S,2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)thiourea

The Diels–Alder cycloadducts of 4-vinylimidazoles and N-phenylmaleimide are shown to undergo facile intermolecular ene reactions. Overall the reaction of three simple molecules (a diene, a dienophile and an enophile) in a two-step process gives 4,5,6,7-tetrahydro-1H-benzo[d]imidazoles with high yields, high atom economy and diastereocontrol of up to 5 new stereocentres.

The Diels–Alder cycloadducts of 4-vinylimidazoles and N-phenylmaleimide are shown to undergo facile intermolecular ene reactions. Overall the reaction of three simple molecules (a diene, a dienophile and an enophile) in a two-step process gives 4,5,6,7-tetrahydro-1H-benzo[d]imidazoles with high yields, high atom economy and diastereocontrol of up to 5 new stereocentres.