RESUMEN

Iron(III) chloride catalyzes the aerobic oxidation of tertiary anilines, including tetrahydroisoquinolines, to form reactive iminium ion intermediates that undergo Mannich reactions with silyloxyfurans, nitroalkanes, and other nucleophiles to give the corresponding butenolides, nitro compounds, and α-substituted tetrahydroisoquinolines, respectively, in good to excellent yields.

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RESUMEN

A general mechanism is proposed for transition metal-catalyzed oxidative Mannich reactions of N,N-dialkylanilines with tert-butyl hydroperoxide (TBHP) as the oxidant. The mechanism consists of a rate-determining single electron transfer (SET) that is uniform from 4-methoxy- to 4-cyano-N,N-dimethylanilines. The tert-butylperoxy radical is the major oxidant in the rate-determining SET step that is followed by competing backward SET and irreversible heterolytic cleavage of the carbon-hydrogen bond at the α-position to nitrogen. A second SET completes the conversion of N,N-dimethylaniline to an iminium ion that is subsequently trapped by the nucleophilic solvent or the oxidant prior to formation of the Mannich adduct. The general role of Rh(2)(cap)(4), RuCl(2)(PPh(3))(3), CuBr, FeCl(3), and Co(OAc)(2) in N,N-dialkylaniline oxidations by T-HYDRO is to initiate the conversion of TBHP to tert-butylperoxy radicals. A second pathway, involving O(2) as the oxidant, exists for copper, iron, and cobalt salts. Results from linear free-energy relationship (LFER) analyses, kinetic and product isotope effects (KIE and PIE), and radical trap experiments of N,N-dimethylaniline oxidation by T-HYDRO in the presence of transition metal catalysts are discussed. Kinetic studies of the oxidative Mannich reaction in methanol and toluene are also reported.

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RESUMEN

A tandem phenol oxidation-Michael addition furnishing oxo- and -aza-heterocycles has been developed. Dirhodium caprolactamate [Rh(2)(cap)(4)] catalyzed oxidation by T-HYDRO of phenols with alcohols, ketones, amides, carboxylic acids, and N-Boc protected amines tethered to their 4-position afforded 4-(tert-butylperoxy)cyclohexa-2,5-dienones that undergo Brønsted acid catalyzed intramolecular Michael addition in one-pot to produce oxo- and -aza-heterocycles in moderate to good yields. The scope of the developed methodology includes dipeptides Boc-Tyr-Gly-OEt and Boc-Tyr-Phe-Me and provides a pathway for understanding the possible transformations arising from oxidative stress of tyrosine residues. A novel method of selective cleavage of O-O bond in hindered internal peroxide using TiCl(4) has been discovered in efforts directed to the construction of cleroindicin F, whose synthesis was completed in 50% yield over just 3 steps from tyrosol using the developed methodology.

RESUMEN

The synthesis of N-aryl-2-carboxyl-3-hydroxy-5-arylpyrroles has been achieved in high yield by the combination of a TBSO-substituted vinyldiazoacetate and nitrones in a one-pot cascade process involving copper-catalyzed Mannich addition, dirhodium-catalyzed dinitrogen extrusion and N-OTBS insertion, and acid-promoted aromatization (elimination).

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RESUMEN

Dirhodium caprolactamate, Rh(2)(cap)(4), is a very efficient catalyst for the generation of the tert-butylperoxy radical from tert-butyl hydroperoxide, and the tert-butylperoxy radical is a highly effective oxidant for phenols and anilines. These reactions are performed with 70% aqueous tert-butyl hydroperoxide using dirhodium caprolactamate in amounts as low as 0.01 mol % to oxidize para-substituted phenols to 4-(tert-butyldioxy)cyclohexadienones. Although these transformations have normally been performed in halocarbon solvents, there is a significant rate enhancement when Rh(2)(cap)(4)-catalyzed phenol oxidations are performed in toluene or chlorobenzene. Electron-rich and electron-poor phenolic substrates undergo selective oxidation in good to excellent yields, but steric influences from bulky para substituents force oxidation onto the ortho position resulting in ortho-quinones. Comparative results with RuCl(2)(PPh(3))(3) and CuI are provided, and mechanistic comparisons are made between these catalysts that are based on diastereoselectivity (reactions with estrone), regioselectivity (reactions with p-tert-butylphenol), and chemoselectivity in the formation of 4-(tert-butyldioxy)cyclohexadienones. The data obtained are consistent with hydrogen atom abstraction by the tert-butylperoxy radical followed by radical combination between the phenoxy radical and the tert-butylperoxy radical. Under similar reaction conditions, para-substituted anilines are oxidized to nitroarenes in good yield, presumably through the corresponding nitrosoarene, and primary amines are oxidized to carbonyl compounds by TBHP in the presence of catalytic amounts of Rh(2)(cap)(4).

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RESUMEN

[reaction: see text] The reduction of benzo-1,2,3,4-tetrazine 1,3-dioxides (BTDOs) 1 with Na(2)S(2)O(4) or SnCl(2) is suggested to proceed via intermediate N-nitrosobenzotriazoles 3 to afford benzotriazoles 2. The (15)N-labeling experiments exhibit that the N-3 atom of the tetrazine ring is incorporated into the nitroso group of 3 that is ultimately released into solution. It is possible that the biological activity of BTDOs is due to their ability to release nitrosating species, i.e., N-nitrosotriazol 3 or HNO(2), in the course of reduction.

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