Regioselective Synthesis of Elusive 4,9-Dihydro-1H-Carbazoles by Gold-Catalyzed Cycloisomerization of 3-Allenylmethylindoles

Abstract

Abstract.A general and efficient synthesis of 4,9-dihydro-1H-carbazoles from 3-allenylmethylindoles is reported. The process, catalyzed by a cationic gold(I) complex, involves a formal C2H bond activation of the indole unit by reaction with allenes. The nature of the substituents at the allylic as well as the terminal position of the allene moiety has a crucial effect on the regioselectivity of the cyclization, which is also influenced by the catalyst and the solvent employed. Moreover, some evidence of the 2 contribution of different reaction routes is provided which led us to propose a plausible multi-pathway mechanism consistent with all the results described.

Catalytic Gold Chemistry: From Simple Salts to Complexes for Regioselective C−H Bond Functionalization

“…[231] The overall reaction consists of treating indolylallenes sequentially with Ph ). [232] The Au(I)-catalyzed intramolecular hydroarylation of indolylallenols was also shown to afford carbazoles in good regioselectivity. Ma et al disclosed the AuCl catalyzed cyclization of 1-(indol-2-yl)-2,3-allenols 250 by a selective 1,2-alkyl or aryl migration via Au-carbene intermediacy 250 a(Scheme 42, Eq.…”

“…On the other hand, Au(I)‐complex with electron‐rich phosphine ligation (Ph 3 PAuNTf 2 ) catalyzed a different reaction course to afford isomeric products 249 via sequential migration/hydroarylation in dichloromethane at low temperature (Scheme 41, Eq. (3)) [232] …”

Gold‐Catalyzed Functionalization Reactions of Indole

“…Early reports on this topic were provided by Wiedenhöfer and by Barluenga, who studied the reactivity of 2-and N-allenylindoles, respectively (Scheme 22). [74] These substrates underwent gold-catalyzed cyclization to afford 4,9-dihydro-1H-carbazoles 63 and 64 with variable regioselectivity according to the substitution pattern of the starting material and the gold(I) catalyst employed (Scheme 24). On the other hand, N-(buta-2,3-dienyl)-indoles 58 underwent 6-endo-dig cyclization to produce dihydropyridoindoles 59.…”

When Indoles Meet Allene and its Derivatives

“…Cationic gold species have promoted the dihydrocarbazole synthesis from compounds 109 , in which indole and allene are separated by one carbon, unraveling a complex reaction mechanism where C3 vs. C2 indole nucleophilicity competes yielding a mixture of carbocyclization products 110 and rearrangement products 111 trough spirocyclic intermediates ( 112 , Scheme 25a). [ 63 ] Similarly, the reaction of indolylallenes 114a , made by Friedel‐Crafts reaction of allenols 113 and indoles, in the presence of gold catalysis at low temperature and an oxidant, gave fully aromatized carbazoles 115 as sole reaction products (Scheme 25b). [ 64 ] Recently, Luna & Almendros described the solvent and temperature‐dependent regioselective reaction of indolylallenes 114b to give spirocycles 116 and carbazole‐type compounds 117 and 118 under heterogeneous catalysis.…”