An Extraordinary Journey with Tert-butyl Nitrite and Diazo Compounds: from Nitrile Oxides to N-heterocycles




De Angelis, Luca

Journal Title

Journal ISSN

Volume Title



Terminal diazo compounds undergo smooth nitrosyl exchange with TBN to furnish nitrile oxides in situ after the loss of molecular nitrogen. Nitrile oxides are very useful reactive synthetic dipoles that dimerize to form furoxans or undergoes [3+2]-cycloaddition with alkenes or alkynes to generate isoxazoles and isoxazolines, respectively, in high yields. A different outcome was observed when vinyldiazo compounds and TBN were used. With these diazo compounds the nitrosonium ion intermediate did not undergo loss of dinitrogen, but instead underwent an intramolecular [5+1]-cycloaddition with the diazonium functionality to form 1,2,3-triazine 1-oxides in high yield. Thermal experiments revealed that the triazine 1-oxides are converted to isoxazoles with loss of dinitrogen in high yields. A new method for the synthesis of 5-alkyl and 5-aryl 1,2,3-triazine compounds was developed through the deoxygenation of triazine 1-oxides with trialkyl phosphites under moderate mild conditions. Based on previously report on the inverse electron demand Diels-Alder (IEDD) on symmetrical 1,2,3-triazine, the reaction occurs through a nucleophilic attack either at 4- or 6-position of the triazine core. Our triazine and triazine 1-oxide allow to differentiate those positions. In particular, the site of addition in triazines 1-oxide is the same that for 1,2,3-triazine in IEDD cycloadditions, and its mechanism occurs by C or N addition at 6-position followed by N2O/N2 elimination and cyclization pathways, but triazine 1-oxide exhibited an enhanced rate of product formation. In the triazine 1-oxide core the site of addition is reversed when TMSN3 was applied, which occurred at 4-position to form enoxime. The hydride from NaBH4 undergoes nucleophilic addition at 6-position on both triazine and triazine 1-oxide to obtain α-amino acid ester and 3,6-dihydro triazine 1-oxide, respectively. Reserve selectivity was observed when Hantzsch ester was used, and the hydride underwent selective nucleophilic addition at 4-position only on the 1,2,3-triazine-1-oxide to form enoxime in high yield and dr ratio. Alkoxides chosen as O-nucleophiles preferred the addition at the 4-position of triazine 1-oxide to obtain an oxime as one single geometrical isomer in high yield. Alternative sites of addition were observed on triazine and triazine 1-oxide when thiolate was used as a nucleophile. The site of nucleophilic addition with PhS- is at 6-position of the triazine, while it is at 4-position of the triazine 1-oxide. In the course of the latter investigations, we discovered that 1,2,3-triazine 1-oxides having an alkyl group containing a C-H bond at the 5-position undergo base promoted rearrangement to vinyldiazo oxime compounds that greatly expands access to diverse vinyldiazoacetates. A different reaction with TBN was observed with enoldiazoacetates. No loss of dinitrogen nor intramolecular cycloaddition was observed. Instead, the equivalent nitrosonium ion intermediate after silyl group-transfer generated unique compounds with 1,2,3,4-oxidized centers having vicinal 1-ester-2-diazo-3-keto-4-oxime functionalities. The treatment diazo oxime compounds with a dirhodium catalyst and water produced α-hydroxy carbonyl derivatives which are rapidly air oxidized to 1-ester-2,3-diketo-4-oxime compounds.


This item is available only to currently enrolled UTSA students, faculty or staff. To download, navigate to Log In in the top right-hand corner of this screen, then select Log in with my UTSA ID.
The full text of this item is not available at this time because the author has placed this item under an embargo until December 12, 2024.