Malonoyl Peroxides Research Articles

1-(((6-(Methoxycarbonyl)-5-oxononan-4-yl)oxy)carbonyl)cyclopropane-1-carboxylic Acid

Here, we first report the 2′-acyloxy-1,3-dicarbonyl compound construction in a three-component oxidative reaction of alkyl ketene dimer with cyclic diacyl peroxide and trimethyl orthoformate. The discovered synthesis allows us to form 2′-functionalized 1,3-dicarbonyl compounds instead of the common 2-functionalized moiety. The reaction between 4-butylidene-3-propyloxetan-2-one and cyclopropyl malonoyl peroxide proceeds in the presence of trifluoroacetic acid and trimethyl orthoformate at 120 °C for 1 h. The synthesized compound was characterized by NMR spectroscopy, mass spectrometry, and IR spectroscopy.

Alkene Syn- and Anti-Oxyamination with Malonoyl Peroxides.

Malonoyl peroxide 6 is an effective reagent for the syn- or anti-oxyamination of alkenes. Reaction of 6 and an alkene in the presence of O-tert-butyl-N-tosylcarbamate (R3 = CO2tBu) leads to the anti-oxyaminated product in up to 99% yield. Use of O-methyl-N-tosyl carbamate (R3 = CO2Me) as the nitrogen nucleophile followed by treatment of the product with trifluoroacetic acid leads to the syn-oxyaminated product in up to 77% yield. Mechanisms consistent with the observed selectivities are proposed.

Alkene Oxyamination Using Malonoyl Peroxides: Preparation of Pyrrolidines and Isoxazolidines.

Treatment of homoallylic N-tosyl amines or allylic N-tosyl hydroxylamines with 1.5 equiv of a malonoyl peroxide provides a stereoselective method to access functionalized pyrrolidines and isoxazolidines. This metal free alkene oxyamination proceeds in 50-85% yield and up to 13:1 trans-selectivity. In addition, the relative stereochemistry of the oxygen and nitrogen substituents can be inverted through an oxidation/reduction sequence or inverting the stereochemistry of the starting alkene. Mechanistic investigations show a higher reactivity for hydroxyl nucleophiles over sulfonamide nucleophiles revealing a preference for dioxygenation over oxyamination.

ChemInform Abstract: Alkene Dioxygenation with Malonoyl Peroxides: Synthesis of γ‐Lactones, Isobenzofuranones, and Tetrahydrofurans.

AbstractThe reaction between homoallylic alcohols or carboxylic acids and malonoyl peroxide provides the title products in moderate to high yields.

Alkene Dioxygenation with Malonoyl Peroxides: Synthesis of γ-Lactones, Isobenzofuranones, and Tetrahydrofurans.

Treatment of homoallylic alcohols or carboxylic acids with malonoyl peroxide 1 provides a stereoselective method for the preparation of tetrahydrofurans, γ-lactones, and isobenzofuranones in 44-82% yield and up to 27:1 trans selectivity. Application of this simple and effective heterocyclization in the synthesis of the antidepressant citalopram is also described.

ChemInform Abstract: Alkene anti‐Dihydroxylation with Malonoyl Peroxides.

Abstract(E)‐Stilbene and (E)‐β‐methylstyrene derivatives as well as various indene and 1,2‐dihydronaphthalene derivatives are efficiently dihydroxylated to form mixtures of the corresponding syn‐ and anti‐diols, which are separated to furnish the anti‐diols in moderate to high yields.

Alkene anti-Dihydroxylation with Malonoyl Peroxides

Malonoyl peroxide 1, prepared in a single step from the commercially available diacid, is an effective reagent for the anti-dihydroxylation of alkenes. Reaction of 1 with an alkene in the presence of acetic acid at 40 °C followed by alkaline hydrolysis leads to the corresponding diol (35-92%) with up to 13:1 anti-selectivity. A mechanism consistent with experimental findings is proposed that accounts for the selectivity observed.

ChemInform Abstract: Arene Oxidation with Malonoyl Peroxides.

AbstractMalonoyl peroxide (II) is found to be an efficient reagent for the oxidation of arenes at room temperature or slightly elevated temperatures to furnish protected phenols.

Arene oxidation with malonoyl peroxides.

Malonoyl peroxide 7, prepared in a single step from the commercially available diacid, is an effective reagent for the oxidation of aromatics. Reaction of an arene with peroxide 7 at room temperature leads to the corresponding protected phenol which can be unmasked by aminolysis. An ionic mechanism consistent with the experimental findings and supported by isotopic labeling, Hammett analysis, EPR investigations, and reactivity profile studies is proposed.

Oxidation of dimethylplatinum(II) complexes with malonyl peroxide derivatives

The reaction of the cyclic peroxides cyclobutane malonoyl peroxide and cyclopentane malonoyl peroxide to dimethylplatinum(II) complexes with the bidentate nitrogen donor ligand 4,4′-di-t-butyl-2,2′-bipyridine (bubpy) gave a mixture of the products of cis and trans oxidative addition, [PtMe2{(O2C)2C(C3H6)}(bubpy)] and [PtMe2{(O2C)2C(C4H8)}(bubpy)], respectively. The cis isomers exist with a chelating dicarboxylate ligand, forming a six-membered ring, while the trans isomers are thought to exist as oligomers, which may react with water or solvent to give complexes containing a monodentate dicarboxylate ligand. Equilibration of the product of cis oxidative addition, cis-[PtMe2{(O2C)2C(C3H6)}(bubpy)], with oxalic or phthalic acid to give equilibria with the oxalate cis-[PtMe2(O4C2)(bubpy)] or phthalate cis-[PtMe2{(O2C)2C6H4}(bubpy)] derivative, respectively, indicated the expected sequence of chelate stability oxalate > cyclobutane malonate > phthalate.

Mechanistic insights into the malonoyl peroxide syn-dihydroxylation of alkenes

A detailed mechanistic understanding of the malonoyl peroxide mediated dihydroxylation of alkenes is presented.

ChemInform Abstract: Alkene Dihydroxylation with Malonoyl Peroxides: Catalysis Using Fluorinated Alcohols.

AbstractA practical two‐step one‐pot procedure is developed for the reaction of alkenes with cyclopropyl malonyl peroxide and subsequent hydrolysis to give syn‐diols.

Alkene Dihydroxylation with Malonoyl Peroxides: Catalysis Using Fluorinated Alcohols

The effect of fluorinated alcohols on the dihydroxylation of alkenes using cyclopropyl malonoyl peroxide is described. Addition of perfluoro-tert-butyl alcohol to a toluene solution of alkene and peroxide increases the rate of product formation and the stereoselectivity observed, providing a simple and effective method for acceleration of this important class of reaction. Basic hydrolysis of the crude reaction mixture provides access to syn-diols in high yield and stereoselectivity.

Metal-Free Dihydroxylation of Alkenes using Cyclobutane Malonoyl Peroxide

Cyclobutane malonoyl peroxide (7), prepared in a single step from the commercially available diacid 6, is an effective reagent for the dihydroxylation of alkenes. Reaction of a chloroform solution of 7 with an alkene in the presence of 1 equiv of water at 40 °C followed by alkaline hydrolysis leads to the corresponding diol (30-84%). With 1,2-disubstituted alkenes, the reaction proceeds with syn-selectivity (3:1 → 50:1). A mechanism consistent with experimental findings is proposed, which is supported by deuterium and oxygen labeling studies and explains the stereoselectivity observed. Alternative reaction pathways that are dependent on the structure of the starting alkene are also described leading to the synthesis of allylic alcohols and γ-lactones.

ChemInform Abstract: Alkene Syn Dihydroxylation with Malonoyl Peroxides.

(E)-Stilbene and (E)-β-methylstyrene derivatives as well as various indene and 1,2-dihydronaphthalene derivatives are efficiently dihydroxylated to form mixtures of the corresponding syn- and anti-diols, which are separated to furnish the anti-diols in moderate to high yields.

Alkene Syn Dihydroxylation with Malonoyl Peroxides

Cyclopropyl malonoyl peroxide (1), which can be prepared in a single step from the commercially available diacid, is an effective reagent for the dihydroxylation of alkenes. Reaction of 1 with an alkene in the presence of 1 equiv of water at 40 °C followed by alkaline hydrolysis leads to the corresponding diol (40-93%). With 1,2-disubstituted alkenes, the reaction proceeds with syn selectivity (3:1 to >50:1). A mechanism consistent with the experimental findings that is supported by oxygen-labeling studies is proposed.

A Convenient Preparation of Malonoylperoxides

Abstract Cyclic Malonoyl peroxides, first reported in 1971 (1) are an important class of compounds for the study of α-lactones (2). These peroxides were prepared by treating a substituted malonic acid with 98% hydrogen peroxide in methanesulfonic acid. A serious disadvantage of this method is the use and the storage of concentrated hydrogen peroxide as well as the remote control device recommended (3) for the operation of this explosive reagent.