Mn(III)‐Based Oxidative Cyclization of Alkenes Using Tricarbonyl System

Abstract

The Mn(III)-based oxidation of 1,1-disubstituted ethenes with 2-(2-aryl-2-oxoethyl)malonates, 2-acetyl-4-aryl-4-oxobutanoates, and 3-acetyl-1-arylpentane-1,4-diones was evaluated. The reaction using the malonates mainly gave the 2,3-dihydro-4Hpyran-4,4-dicarboxylates along with g-lactones. A similar reaction using the acetyloxobutanoates and acetylpentanediones produced the 2,3,3a,6a-tetrahydrofuro[2, 3-b]furans and the corresponding dihydropyrans. The cyclization was strongly affected by the nucleophilicity of the carbonyl oxygen in the carbocation intermediate, and the kinetic and thermodynamic controls of the following reaction. The structure determination and the mechanisms are discussed.[a] T.

Multidecagram Scale Synthesis of an Endoperoxide, Precursor of Anti-malarial and Anti-leishmanial Agents, via Free-Radical [2 + 2 + 2] Annulation with Molecular Oxygen

“…Moreover, an excess of the oxidizable substrate might help to avoid a possible competitive oxidation of the reaction product . In fact, most of the Mn-based protocols furnishing endoperoxides involve a large excess of β-ketoester. − In our case, it is noteworthy that the best result (75% yield) was obtained employing only a slight excess of methyl acetoacetate (1.5 equiv). The model derived from the DoE study indicates that the excess of β-ketoester 1 does not have relevant consequences on the reaction outcome; therefore, we decided to proceed with the reaction scale-up employing only 1 equiv of substrate 1 aiming to decrease the process costs, mass intensity, and to facilitate the product purification.…”

Rearrangement of Methylenebis(cyclohexane-1,3-dione) Enols Induced by Mn(III)-Catalyzed Aerobic Oxidation

“…Among them, 1,3-dicarbonyl enolates are the most powerful and convenient chemical species for organic synthesis . We have studied the chemistry of the 1,3-dicarbonyl enolate radicals produced by Mn­(III)-mediated oxidation and synthesized many unique organic molecules. , Recently, we reported carbon–carbon bond formation and cyclization using the reactions of tricarbonyl and tetracarbonyl systems, for example, the reaction of 2-oxoethyl-1,3-dicarbonyl compounds with alkenes, which produced dihydropyrans and tetrahydrofuro­[2,3- b ]­furans, and the reaction of methylenebis­(cyclohexanedione)­s, which selectively gave spirodihydrofurans and dispirocyclopropanes . On the other hand, the Mn­(III)-catalyzed aerobic oxidation of 1,3-dicarbonyl enolates led to endoperoxidation and hydroperoxidation reactions .…”