Gold‐Catalyzed Cyclization of 1‐(Indol‐3‐yl)‐3‐alkyn‐1‐ols: Facile Synthesis of Diversified Carbazoles

Abstract

Efficient cyclization of 1-(indol-3-yl)-3-alkyn-1-ols in the presence of a cationic gold(I) complex, leading to annulated or specific substituted carbazoles, was observed. Depending on the reaction conditions and substitution pattern, divergent reaction pathways were discovered, furnishing diversified carbazole structures. Cycloalkyl-annulated [b]carbazoles are obtained through 1,2-alkyl migration of the metal-carbene intermediates; cycloalkyl-annulated [a]carbazoles are formed through a Wagner-Meerwein-type 1,2-alkyl shift; carbazole ethers are constructed through ring-opening of the cyclopropyl group by nucleophilic attack of water or an alcohol.

[1, 2]‐Migration Reactions Catalyzed by Gold Complexes and their Applications in Total Synthesis

“…Shi and co‐workers described the cyclization of 2,2‐disubstituted 1‐(indol‐3‐yl)‐3‐alkyn‐1‐ols, forming annulated and highly substituted carbazoles . As shown in Scheme , the reaction provides a mixture of two regioisomers (e. g., 22 and 23 ).…”

Regioselective Direct C‐Alkenylation of Indoles

“…A similar migration process is observed in the Au I ‐catalyzed intramolecular reaction of 1‐(indol‐3‐yl)‐3‐alkyn‐1‐ols bearing a cyclopropyl substituent which ultimately leads to the formation of carbazole derivatives embedding a four membered ring (Scheme ) . After the cyclization of the activated alkyne 40 the obtained spiroindole 41 undergoes to a selective migration reaction leading to tetrahydrocarbazole intermediate 42 .…”

“…As imilar migration process is observedi nt he Au I -catalyzed intramolecular reactiono f1 -(indol-3-yl)-3-alkyn-1-ols bearinga cyclopropyls ubstituent which ultimately leads to the formation of carbazole derivatives embedding af our membered ring (Scheme 44). [105] After the cyclization of the activated alkyne 40 the obtained spiroindole 41 undergoes to aselective migration reaction leading to tetrahydrocarbazole intermediate 42.Protonation of the hydroxy group and subsequent dehydration leads to intermediate 43 which upon ring enlargement provides the tetracyclic cation 44.T he final product is obtained by deauration of the six-membered ring which regenerates the catalyst. Replacing dichloromethane with methanol, it is possible to prepare 2-methoxyethylcarbazoles arising from ac leavage of the cyclopropyl ring on intermediate 43.…”

Catalyst‐Dependent Divergent Synthesis of Pyrroles from 3‐Alkynyl Imine Derivatives: A Noncarbonylative and Carbonylative Approach

“…Inspired by the study of Toste and co-workers, we assumed that if the azide group was replaced by an imino functionality, an a-(azomethineylide)-metal carbenoid could be generated through the third mode shown in Scheme 1, and this would provide an atom-economic and safer route to multisubstituted pyrroles. The difficulties mainly lie in the regioselectivity [10] (Scheme 2, this work). On the other hand, cyclopropylimines [11] are very useful five-atom synthons in organic chemistry and their reactivities are quite similar to vinylcyclopropanes (VCPs).…”