Formation and Intramolecular Capture of α-Imino Gold Carbenoids in the Au(I)-Catalyzed [3 + 2] Reaction of Anthranils, 1,2,4-Oxadiazoles, and 4,5-Dihydro-1,2,4-Oxadiazoles with Ynamides

Abstract

α-Imino gold carbenoid species have been recognized as key intermediates in a plethora of processes involving gold-activated alkynes. Here, we explored the pathways of the Au(I)-catalyzed [3 + 2] reaction between the mild nucleophiles: anthranil, 1,2,4-oxadiazole, or 4,5-dihydro-1,2,4-oxadiazole, and an ynamide, PhC≡C-N(Ts)Me, proceeding via the formation of the aforementioned α-imino gold carbene intermediate which, after intramolecular capture, regioselectively produces 2-amino-3-phenyl-7-acyl indoles, N-acyl-5-aminoimidazoles, or N-alkyl-4-aminoimidazoles, respectively. In all cases, the regioselectivity of the substituents at 2, 3 in the 7-acyl-indole ring and 4, 5 in the substituted imidazole ring is decided at the first transition state, involving the attack of nitrogen on the C1 or C2 carbon of the activated ynamide. A subsequent and steep energy drop furnishes the key α-imino gold carbene. These features are more pronounced for anthranil and 4,5-dihydro-1,2,4-oxadiazole reactions. Strikingly, in the 4,5-dihydro-1,2,4-oxadiazole reaction the significant drop of energy is due to the formation of an unstable α-imino gold carbene, which after a spontaneous benzaldehyde elimination is converted to a stabilized one. Compared to anthranil, the reaction pathways for 1,2,4-oxadiazoles or 4,5-dihydro-1,2,4-oxadiazoles are found to be significantly more complex than anticipated in the original research. For instance, compared to the formation of a five-member ring from the α-imino gold carbene, one competitive route involves the formation of intermediates consisting of a four-member ring condensed with a three-member ring, which after a metathesis and ring expansion led to the imidazole ring.

Comprehensive Overview of Homogeneous Gold-Catalyzed Transformations of π-Systems for Application Scientists

“…Then, divergent steps are observed through a nucleophilic attack at the metal-coordinated carbocation of 56d or 56d favoring a 1,5-cyclization forming 2-aminopyrrole 56g for the gold catalyst or 1,7-cyclization forming 1,3-oxazepine 56i (Scheme 56). We have confirmed these mechanistic steps for the Au(I)-catalyzed reaction between 1,2,4-oxadiazoles and ynamides [44].…”

“…Then, divergent steps are observed through a nucleophilic attack at the metal-coordinated carbocation of 56d or 56d′ favoring a 1,5-cyclization forming 2-aminopyrrole 56g for the gold catalyst or 1,7-cyclization forming 1,3-oxazepine 56i′ (Scheme 56). We have confirmed these mechanistic steps for the Au(I)-catalyzed reaction between 1,2,4-oxadiazoles and ynamides [44]. [138] versus Pt(II)-catalyzed [139] reaction between an isoxazole 56a and ynamide 56b, leading to 2-aminopyrrole 56g or 1,3-oxazepine 56i , respectively Ye 2015, 2017) [138,139].…”

“…In another paper, we also compared [44] the reaction between anthranil, 1,2,4-oxadiazole, or 4,5-dihydro-1,2,4-oxadiazole, and the ynamide, PhC≡C-N(Ts)Me, to afford proceeding via the formation of the aforementioned α-imino gold carbene intermediate, which, after intramolecular capture, regioselectively produced 2-amino-3-phenyl-7-acyl indoles, N-acyl-5-aminoimidazoles, or N-alkyl-4-aminoimidazoles, respectively. In all cases, the regioselectivity of the substituents at 2, 3 in the 7-acyl-indole ring and 4, 5 in the substituted imidazole ring is decided at the first transition state, involving the attack of nitrogen on the C1 or C2 carbon of the activated ynamide.…”

Metal-catalyzed Markovnikov-type selective hydrofunctionalization of terminal alkynes

“…Currently, there are two main modes for synthesizing alkenyl halides from alkynes. [165][166][167][168] The first is to use low-valent metals with strong reducing properties to be oxidized by H-X bond in acids, such as hydrochloric acid, hydrobromic acid, and hydriodic acid, to form new metal-hydride bonds and metal-halogen bonds. Alkynes are then inserted into the metal-hydrogen bonds to generate the corresponding alkenyl metal compounds then undergo reductive elimination to obtain a-alkenyl halides (as shown in mode a, Scheme 2).…”