Gold‐Catalyzed CH Annulation of Anthranils with Alkynes: A Facile, Flexible, and Atom‐Economical Synthesis of Unprotected 7‐Acylindoles

Abstract

The gold-catalyzed C-H annulation of anthranil derivatives with alkynes offers a facile, flexible, and atom-economical one-step route to unprotected 7-acylindoles. An intermediate α-imino gold carbene, generated by an intermolecular reaction, promotes ortho-aryl C-H functionalization to afford the target products. The transformation proceeds with a broad range of substrates under mild conditions. Moreover, the obtained functionalized indole products represent a versatile platform for the construction of diverse indolyl frameworks.

Diverting Reactive Intermediates Toward Unusual Chemistry: Unexpected Anthranil Products from Davis–Beirut Reaction

“…15–19 Recently, the transformation of anthranils to other heterocycles have found use in complex molecule synthesis. 20 The utility of this heterocycle, coupled with our group’s long-standing interest in heterocycle-to-heterocycle strategies, 21 prompted us to investigate this route to anthranils.…”

Gold‐Catalyzed [4+2] Annulation/Cyclization Cascades of Benzisoxazoles with Propiolate Derivatives to Access Highly Oxygenated Tetrahydroquinolines

“…Quinoline oxides (3)a re versatile intermediates for delivering oxygenated quinoline derivatives because of their epoxide functionality.A ss hown in Scheme 1, LiAlH 4 reductions of 3a afforded the alcohol 8a as as ingle diastereomer, and the structure of this diol derivative was determined by 1 HNOE spectroscopy.R emoval of the epoxide in 3a was achieved with Pd/C/H 2 in MeOH, thus yielding the quinoline derivative 3a H in 75 %yield. Ther eactions were also compatible with various benzisoxazoles substituted with X = Cl, Br, and OCO 2 Et, as well as Y = Cl, and the corresponding products 7f-i were obtained efficiently (entries [5][6][7][8]. Particularly notable is Zn(OTf) 2 -catalyzed hydrative cyclizations of 3a in DCE.…”

“…[4] Thec urrent syntheses of these bioactive molecules rely on diverse and long procedures. [6] Theu se of NÀOcontaining nucleophiles is av iable route to access valuable azacyclic frameworks.T he groups of Ye [7] and Hashmi [8] reported interesting [3+ +2] annulations of isoxazoles and benzisoxazoles with electron-rich ynamides,t hereby yielding substituted pyrrole derivatives chemoselectively [ Figure 2, Eq. [6] Theu se of NÀOcontaining nucleophiles is av iable route to access valuable azacyclic frameworks.T he groups of Ye [7] and Hashmi [8] reported interesting [3+ +2] annulations of isoxazoles and benzisoxazoles with electron-rich ynamides,t hereby yielding substituted pyrrole derivatives chemoselectively [ Figure 2, Eq.…”

Development of Gold‐catalyzed [4+1] and [2+2+1]/[4+2] Annulations between Propiolate Derivatives and Isoxazoles

“…[1] These reactions focus intensively on electron-rich ynamides, [2] and recently on electron-deficient propiolates. [4] Because of their easy synthesis,i soxazoles prove to be versatile three-atom building units in various catalytic annulations, [5][6][7] thus yielding useful azacycles with molecular complexity.Manning and Davies reported the first instance in rhodium-catalyzed [3+ +3] annulations of isoxazoles with alkenyldiazo species to afford highly substituted 3-carbonylpyridine derivatives. [4] Because of their easy synthesis,i soxazoles prove to be versatile three-atom building units in various catalytic annulations, [5][6][7] thus yielding useful azacycles with molecular complexity.Manning and Davies reported the first instance in rhodium-catalyzed [3+ +3] annulations of isoxazoles with alkenyldiazo species to afford highly substituted 3-carbonylpyridine derivatives.…”

“…[5a] In the context of ynamides,Y ea nd co-workers report as eries of catalytic [3+ +2] annulations to access 4-carbonyl-2-aminopyrroles [Eq. [7] These annulations involve an Nattack to generate gold iminocarbenes to facilitate aza-Nazarov reactions [Eqs. [6] Hashmi and coworkers reported distinct [3+ +2] annulations of ynamides with benzo[c]isoxazoles to ].…”