Synthesis of Polycyclic Indole Skeletons by a Gold(I)‐Catalyzed Cascade Reaction

Abstract

The conversion of simple, easily available urea-substituted 3-phenylpropargyl alcohols catalyzed by a simple IPr-gold(I) catalyst in a gold(I)-catalyzed cascade reaction composing of a gold-catalyzed nucleophilic addition and a subsequent gold-catalyzed substitution reaction delivers 1H-imidazo[1,5-a]indol-3(2H)-ones. Other gold(I) catalysts or silver catalysts gave lower yields and often gave other side products. Gold(III) and copper(II) catalysts decomposed the starting material. Twelve examples, including donor and acceptor substituents on the distal nitrogen of the urea substructure, are provided. An X-ray crystal structure analysis confirmed the structural assignment. The mechanistic investigation including isolation and further conversion of intermediates and reactions with enantiopure starting materials indicated that after the nucleophilic-addition step, the substrate undergoes an S(N)1-type benzylic substitution reaction at the indolyl alcohol intermediate or an intramolecular hydroamination reaction of the 2-vinylindole intermediate.

Gold(I)-Catalyzed Activation of Alkynes for the Construction of Molecular Complexity

“…1 H -Imidazol-[1,5- a] indol-3(2 H )-ones were also prepared in the presence of a gold(I) catalyst starting from urea derivatives. 145 …”

Homogeneous Gold‐Catalyzed Cyclization Reactions of Alkynes with N‐ and S‐Nucleophiles

“…This nucleophilic vinylgold species 109 then added across the carbonyl function with formation of a 7‐membered ring, which promoted another dehydration, 1,3‐proton transfer and protodeauration 81,82. Based on these results Hashmi and co‐workers developed a method to convert ureas 111 into polycyclic indole scaffolds 112 (Scheme ) 83…”

A practical Cu(I)-catalyzed domino approach to 1,2-disubstituted indoles and its application for the assembly of indolophenanthridines

“…[14][15][16] Several one-pot synthetic protocols have also been developed recently. [17][18][19] In spite of these remarkable progresses, many of the previous methods require expensive and/or sensitive catalysts (such as Pd and Au salts) or special substrates such as 1-or 2-substituted indoles and o-(gem-dihalovinyl)anilines. The annulation of N-substituted 2-alkynylanilines [20][21][22] and the coupling/cyclization of 2-alkynyl halobenzenes with primary amines [23][24][25] can also generate 1,2-disubstituted indoles.…”