Nucleophile-Controlled Trapping of Gold Carbene by Nitriles and Water: Synthesis of 5H-Pyrimido[5,4-b]indoles and 2-Benzylidene-3-indolinones

Abstract

A gold-catalyzed, nucleophile-controlled cascade reaction of N-(2-azidophenyl-ynyl)methanesulfonamides with nitriles and water is described that provides structurally diverse 5H-pyrimido[5,4-b]indoles and 2-benzylidene-3-indolinones in good to excellent yields. Mechanistic studies indicate that the βsulfonamido-α-imino gold carbene is the key intermediate which is generated through the gold-catalyzed cyclization of N-(2azidophenyl-ynyl)methanesulfonamides and undergoes formal [4 + 2] cascade annulation with nitriles and intramolecular S N 2′ type reaction with water, respectively.

Scaffold-Hopping Strategies in Aurone Optimization: A Comprehensive Review of Synthetic Procedures and Biological Activities of Nitrogen and Sulfur Analogues

“…More recently, the novel gold-catalyzed Method VI was described in the literature [ 31 ]. This approach entails the nucleophile-controlled trapping of a gold carbene intermediate by water.…”

“…This approach entails the nucleophile-controlled trapping of a gold carbene intermediate by water. In detail, the β-sulfonamido-α-imino gold carbene, generated by the gold-catalyzed (tBuXPhosAuNTf 2 ) 5-endo-dig cyclization of the N-(2-azidophenyl-ynyl)methanesulfonamide 10 , is captured by water through a concerted intramolecular SN 2 ’ reaction to give the final azaaurone core [ 31 ].…”

“…More limited applications and fewer substituents explored. [30,31] On the other hand, the recently proposed protocols IV-VI give the opportunity of a one-pot coordinated synthesis by exploiting a finer transition organometallic catalysis. Such an approach undoubtedly has a positive impact on the overall yield and reaction times.…”

“…[ 30,31] 2.1.2. Synthetic Procedures: Scaffold Elaboration By exploiting the high versatility of these compounds, other interesting synthetic methods for modifying the azaaurone scaffold have been reported in the literature, providing interesting building blocks for the identification of new biologically active derivatives and further alternatives for SAR exploration.…”