Acyl Migration versus Epoxidation in Gold Catalysis: Facile, Switchable, and Atom‐Economic Synthesis of Acylindoles and Quinoline Derivatives

Abstract

We report a switchable synthesis of acylindoles and quinoline derivatives via gold‐catalyzed annulations of anthranils and ynamides. α‐Imino gold carbenes, generated in situ from anthranils and an N,O‐coordinated gold(III) catalyst, undergo electrophilic attack to the aryl π‐bond, followed by unexpected and highly selective 1,4‐ or 1,3‐acyl migrations to form 6‐acylindoles or 5‐acylindoles. With the (2‐biphenyl)di‐tert‐butylphosphine (JohnPhos) ligand, gold(I) carbenes experienced carbene/carbonyl additions to deliver quinoline oxides. Some of these epoxides are valuable substrates for the preparation of 3‐hydroxylquinolines, quinolin‐3(4H)‐ones, and polycyclic compounds via facile in situ rearrangements. The reaction can be efficiently conducted on a gram scale and the obtained products are valuable substrates for preparing other potentially useful compounds. A computational study explained the unexpected selectivities and the dependency of the reaction pathway on the oxidation state and ligands of gold. With gold(III) the barrier for the formation of the strained oxirane ring is too high; whereas with gold(I) this transition state becomes accessible. Furthermore, energetic barriers to migration of the substituents on the intermediate sigma‐complexes support the observed substitution pattern in the final product.

Nitrene Transfer and Carbene Transfer in Gold Catalysis

“…In a proposed mechanistic cycle (Scheme 76 A highly selective and ligand-dependent protocol was developed by Hashmi and co-workers, involving a gold(III)catalyzed (3 + 2) annulation between ynamides 163 and 7methyl anthranils 164 to deliver either 6-acylindoles 165 or 5acylindoles 166 depending on the C5 substitution pattern on the anthranil ring (Scheme 77). 96 Computational results indicated a clockwise migration of an acyl group on the aromatic ring to furnish these two distinct products 165 and 166. Moreover, a nucleophilic attack of the anthranil aryl π-bond on the typical αimino gold carbene intermediate 163 In the same report, a divergent synthesis of quinoline oxides 169 from similar ynamides 167 and anthranils 168 through a carbonyl/carbene addition was presented by Hashmi and coworkers on switching to a gold(I) catalytic system (Scheme 79).…”

Monitoring of the Pre-Equilibrium Step in the Alkyne Hydration Reaction Catalyzed by Au(III) Complexes: A Computational Study Based on Experimental Evidences

“…The study of Au(III) chemistry is much more challenging both experimentally and theoretically, because these complexes are usually very reactive and difficult to synthesize. However, in recent years, many studies on the catalytic efficiency of Au(III) have been carried out, motivated by the expected more efficient activation of double and triple C-C bonds due to the larger Lewis acidity of the metal in its +3 oxidation state [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. First studies were devoted to synthesize stable Au(III) complexes.…”

Dichotomy of platinum(II) and gold(III) carbene intermediates switching from N- to O-selectivity

“…See Supplementary Information for computational details). Since the mechanism for the generation of Au/Pt carbene is similar to those of previous analogous reports 35 , 41 , here we do not discuss it but give the corresponding energetic details in Supplementary Information (Figs. S2 , S3 ).…”

“…However, the study of gold(III) carbene analogues that behave and react distinctly to gold(I) carbenes has been realized seldom. Very recently, in the reaction of ynamides with 7-methylanthranil the cyclization pathway of gold carbene intermediate depends on ligands but also the oxidation state of gold 35 . While gold(I) carbenes were facilely trapped by the oxygen atom of aldehyde (Fig.…”