title: Ruthenium-Catalyzed C-H Bond Activation Approach to Azolyl Aminals and Hemiaminal Ethers, Mechanistic Evaluations, and Isomer Interconversion.
abstract: C(sp3)-N bond-forming reactions between benzotriazole and 5,6-dimethylbenzotriazole withN-methylpyrrolidinone, tetrahydrofuran, tetrahydropyran, diethyl ether, 1,4-dioxane, and isochroman have been conducted using RuCl3•3H2O/t-BuOOH in 1,2-dichloroethane. In all cases,N1 andN2 alkylation products were obtained, and these are readily separated by chromatography. One of these products, 1-(isochroman-1-yl)-5,6-dimethyl-1H-benzotriazole, was examined by X-ray crystallography. It is the first such compound to be analyzed by this method, and notably, the benzotriazolyl moiety is quasi-axially disposed, consistent with the anomeric effect. This has plausible consequences, not observed previously. In contrast to other hemiaminal ether-forming reactions, which proceed via radicals, this Ru-catalyzed process is not suppressed in the presence of a radical inhibitor. Therefore, an oxoruthenium-species-mediated rapid formation of an oxocarbenium intermediate is believed to occur. In the radical-trapping experiment, previously unknown products containing both the benzotriazole and the TEMPO unit have been identified. In these products, it is likely that the benzotriazole is introduced via a Ru-catalyzed C-N bond formation, whereas C-O bond-formation with TEMPO occurs via a radical reaction. We show that reactions of THF with TEMPO are influenced by ambient light. A competitive reaction of THF and THF-d8with benzotriazole indicated that C-H bond cleavage occursca.5 times faster than C-D cleavage. This is comparable to other metal-mediated radical reactions of THF, but lower than that observed for a reaction catalyzed byn-Bu4N+I-. Detailed mechanistic experiments and comparisons are described. The catalytic system was also evaluated for reactions of benzimidazole, imidazole, 1,2,4-triazole, and 1,2,3-triazole with THF, and successful reactions were achieved in each case. In the course of our studies, we discovered an unexpected but significant isomerization of some of the benzotriazolyl hemiaminal ethers. This is plausibly attributable to the pseudoaxial orientation of the heterocycle in the products and the stability of oxocarbenium ions, both of which can contribute to C-N bond cleavage and reformation. Predominantly, theN2-isomers rearrange to theN1-isomerseven upon storage at low temperature!This previously unknown phenomenon has also been studied and described.
authors: Department of Chemistry, The City College of New York, 160 Convent Avenue, New York, NY 10031, United States; The Ph.D. Program in Chemistry, The Graduate Center of The City University of New York, New York, NY 10016, United States.
authors: Manish K
authors: MK
authors: Singh
authors: Department of Chemistry, The City College of New York, 160 Convent Avenue, New York, NY 10031, United States; The Ph.D. Program in Chemistry, The Graduate Center of The City University of New York, New York, NY 10016, United States.
authors: Hari K
authors: HK
authors: Akula
authors: Department of Chemistry, The City College of New York, 160 Convent Avenue, New York, NY 10031, United States.
authors: Sakilam
authors: S
authors: Satishkumar
authors: Department of Chemistry, The University of North Dakota, 151 Cornell Street Stop 9024, Grand Forks, ND 58202, United States.
authors: Lothar
authors: L
authors: Stahl
authors: Department of Chemistry, The City College of New York, 160 Convent Avenue, New York, NY 10031, United States; The Ph.D. Program in Chemistry, The Graduate Center of The City University of New York, New York, NY 10016, United States.
authors: Mahesh K
authors: MK
authors: Lakshman
keywords: C–H bond activation; N-methylpyrrolidinone; aminal; azole; ether; hemiaminal ether; ruthenium catalysis