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
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, an...
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MDPI AG
2022-08-01
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| author | Ioannis Stylianakis Iraklis Litinas Antonios Kolocouris Carlos Silva López |
| author_facet | Ioannis Stylianakis Iraklis Litinas Antonios Kolocouris Carlos Silva López |
| author_sort | Ioannis Stylianakis |
| collection | DOAJ |
| description | 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, <i>N</i>-acyl-5-aminoimidazoles, or <i>N</i>-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. |
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| language | English |
| last_indexed | 2024-03-09T09:59:32Z |
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| spelling | doaj.art-7be3698205054502aa3816040e80ee132023-12-01T23:33:04ZengMDPI AGCatalysts2073-43442022-08-0112891510.3390/catal12080915Formation 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 YnamidesIoannis Stylianakis0Iraklis Litinas1Antonios Kolocouris2Carlos Silva López3Laboratory of Medicinal Chemistry, Section of Pharmaceutical Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens Panepistimiopolis Zografou, 15771 Athens, GreeceLaboratory of Medicinal Chemistry, Section of Pharmaceutical Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens Panepistimiopolis Zografou, 15771 Athens, GreeceLaboratory of Medicinal Chemistry, Section of Pharmaceutical Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens Panepistimiopolis Zografou, 15771 Athens, GreeceDepartamento de Química Orgánica, Facultad de Química, Universidad de Vigo, Campus Lagoas-Marcosende, 36310 Vigo, Spainα-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, <i>N</i>-acyl-5-aminoimidazoles, or <i>N</i>-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.https://www.mdpi.com/2073-4344/12/8/915Au(I) catalysis[3 + 2] additionα-imino gold carbeneN-heterocyclesalkyne activation |
| spellingShingle | Ioannis Stylianakis Iraklis Litinas Antonios Kolocouris Carlos Silva López 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 Catalysts Au(I) catalysis [3 + 2] addition α-imino gold carbene N-heterocycles alkyne activation |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Au(I) catalysis [3 + 2] addition α-imino gold carbene N-heterocycles alkyne activation |
| url | https://www.mdpi.com/2073-4344/12/8/915 |
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