The radical-chain addition of aldehydes to alkenes by the use of N-hydroxyphthalimide (NHPI) as a polarity-reversal catalyst

Hydroacylation of simple alkenes with aldehydes via a radical process was successfully achieved by the use of N-hydroxyphthalimide (NHPI) as a polarity-reversal catalyst. Thus, 5-tridecanone was obtained by the reaction of oct-1-ene with pentanal in the presence of small amounts of NHPI and dibenzoyl peroxide (BPO).     

Rhodium(II) catalyzed highly diastereoselective synthesis of conformationally restricted dispiro[1,3-dioxolane]bisoxindoles

Synthesis of conformationally restricted dispiro- and bis-dispiro-1,3-dioxolanes via three-component reaction of diazoamides, ketoamides/diketones, and aromatic/heteroaromatic aldehydes in the presence of rhodium(II) acetate dimer catalyst at room temperature involving carbonyl ylides is demonstrated with diastereoselectivity. Synthesis of macrocyclic dispiro-1,3-dioxolanes via intramolecular carbonyl ylide is also delineated in high yield. The conformationally restricted symmetrical as well as unsymmetrical dispiro-1,3-dioxolanes were obtained under mild conditions in a highly diastereo- and regioselective manner.     

Julia–Kocienski approach to trifluoromethyl-substituted alkenes

A Julia–Kocienski approach to trifluoromethyl-substituted alkenes was evaluated in the reactions of 1,3-benzothiazol-2-yl, 1-phenyl-1H-tetrazol-5-yl, and 1-tbutyl-1H-tetrazol-5-yl 2,2,2-trifluoroethyl sulfones with aldehydes. Among the various conditions tested, the best yields were obtained with 1-phenyl-1H-tetrazol-5-yl 2,2,2-trifluoroethyl sulfone, in CsF-mediated, room temperature olefinations in DMSO. Aromatic aldehydes gave (trifluoromethyl)vinyl derivatives in 23–86% yields, with generally moderate stereoselectivity. Straightforward synthesis of the Julia–Kocienski reagent, and conversion to trifluoromethyl-substituted alkenes under mild reaction conditions, are the advantages of this approach.     

Intermolecular reactions of chlorohydrine anions: acetalization of carbonyl compounds under basic conditions

[reaction: see text] Nonenolizable aldehydes and ketones react with 2-chloroethanol and 3-chloropropanol under basic conditions (t-BuOK, DMF/THF) with formation of 2-substituted 1,3-dioxolanes and 1,3-dioxanes, respectively. Conversion of the two-step addition-alkylation process depends on the electrophilicity of the carbonyl group that governs the equilibrium of addition of chloroalkoxides. This method of protection of carbonyl groups in the form of cyclic acetals under kinetically controlled conditions is complementary to the acid-catalyzed reaction with diols.     

On the preparation of 2-halo alkyl substituted 1,3-dioxolanes and 1,3-dioxanes

Several methods for the preparation of 2-perfluoromethyl-substituted 1,3-dioxolanes and 1,3-dioxanes were tried. The method of Nerdel for the preparation of 1,3-dioxolanes, making use of the condensation between carbonyl compounds and oxiranes, was found to be suitable for perhalogenated ketones and aldehydes, and may even be extended to oxetanes, affording 2-perhaloalkylated 1,3-dioxanes.The yield of the cyclic acetals drops with inreasing substitution.     

The formation of novel 1,3-dioxolanes: atypical Baylis-Hillman reaction of a sesquiterpene lactone parthenin

The Baylis-Hillman reaction of a sesquiterpene lactone parthenin with various aldehydes gave unexpected products containing a 1,3-dioxolane moiety. Both small aliphatic and aromatic aldehydes produced 1,3-dioxolanes, whereas higher aliphatic aldehydes produced normal Baylis-Hillman products.     

Synthesis of aromatic aldehydes by aerobic oxidation of hydroaromatic compounds and diarylalkanes using N-hydroxyphthalimide (NHPI) as a key catalyst

Aerobic oxidation of hydroaromatic compounds and diarylalkanes by N-hydroxyphthalimide (NHPI) under mild conditions afforded the corresponding hydroperoxides in high selectivity. Treatment of the resulting hydroperoxides with sulfuric acid followed by neutralization by a base resulted in phenol and aromatic aldehydes in high selectivity. This method provides a convenient synthetic route to aldehydes involving an aromatic moiety.     

A novel approach of cycloaddition of difluorocarbene to alpha,beta-unsaturated aldehydes and ketones: synthesis of gem-difluorocyclopropyl ketones and 2-fluorofurans

A series of gem-difluorocyclopropyl acetals and ketals are easily obtained in moderate yields from the [1 + 2] cycloaddition of difluorocarbene to 1,3-dioxolanes of alpha,beta-unsaturated aromatic aldehydes and ketones. Hydrolysis of these fluorinated compounds under acidic conditions either gives the corresponding gem-difluorocyclopropyl ketones or 1-aryl-2-fluorofuran derivatives through intramolecular carbonium rearrangement with simultaneous ring cleavage.     

Catalytic oxyalkylation of alkenes with alkanes and molecular oxygen via a radical process using N-hydroxyphthalimide

A novel catalytic method for the radical addition of alkanes and molecular oxygen to electron-deficient alkenes was achieved by the use of N-hydroxyphthalimide (NHPI) combined with a Co species as the catalyst. This reaction is referred to as oxyalkylation of alkenes with alkanes and O(2). For instance, the reaction of 1,3-dimethyladamantane with methyl acrylate under molecular oxygen in the presence of catalytic amounts of NHPI and Co(acac)(3) at 70 degrees C for 16 h gave oxyalkylated products in 91% yield. Other alkenes such as fumarate and acrylonitrile also serve as good acceptors of alkyl radicals and O(2) to afford the corresponding adducts in high yields. The generality of the present reaction was examined between various alkanes and alkenes under dioxygen. The behavior of Co ions during the reaction course was discussed. The present reaction involves (i) an alkyl radical generation via hydrogen abstraction of alkane by phthalimide N-oxyl generated in situ from NHPI and O(2) assisted by Co(II), (ii) the addition of the resulting alkyl radical to an electron-deficient alkene to form an adduct radical, (iii) trapping of the adduct radical by O(2) yielding a hydroperoxide, and (iv) the decomposition of the hydroperoxide by Co ions to form an adduct in which a hydroxy or a carbonyl function is incorporated.     

Novel and efficient approach to (Z)-4-trifluoroethylidene-1,3-dioxolane derivatives via (trifluoromethyl)ethynylation of ketones and aldehydes

Perfluoroalkylated 4-trifluoroethylidene-1,3-dioxolanes 2a-p were prepared in quantitative yields from the reaction of new stable (trifluoromethyl)ethynylation reagent 1a with TBAF at −15 °C for 10 min, followed by treatment with phenyl perfluoroalkylated ketones at room temperature. The use of aldehydes under the same reaction condition afforded 1,3-dioxolanes 2q-r in good yields. The reaction of 1a with TBAF, followed by treatment with aldehydes or ketones at −15 °C for 10 min and then with trifluoroacetophenone at room temperature provided 1,3-dioxolane derivatives 2s-t in good yields. Tetrabutylammonium trifluoropropynylide [II] was treated with benzaldehyde derivatives at −15 °C for 10 min, followed by treatment with trifluoroacetophenone, to give the corresponding 1,3-dioxolanes 2u-z and 1,3-dioxines 3u-z with different reaction condition.     

Lewis acid catalyzed carbon-carbon bond cleavage of aryl oxiranyl diketones: synthesis of cis-2,5-disubstituted 1,3-dioxolanes

Carbonyl ylide is one of the most important intermediates which can undergo a series of 1,3-dipolar cycloaddition reactions. The C-C heterolysis of oxirane is believed to be the most atom-economic and straightforward way to generate carbonyl ylide. However, this chemistry was only achieved under photochemical and thermal conditions in past years. In this work, the one-step diastereoselective synthesis of cis-2,5-disubstituted 1,3-dioxolanes via [3 + 2] cycloadditions of aldehydes and carbonyl ylide, which is obtained from Lewis acid catalyzed C-C bond heterolysis of aryl oxiranyl diketones at ambient temperature, is described.     

Generation of Carbenes by Photochemical Cycloelimination

A wide variety of shelf stable substrates undergo photochemical cycloelimination under relatively mild conditions. Suitable substrates include cyclopropanes, oxiranes, aziridines, and diazirines, as well as 3 H-pyrazoles and 1,3-dioxolanes. Carbenes prepared from these substrates as well as certain cyclic carbonates, sulfites, and phosphoranes behave chemically in a manner similar to divalent carbon species produced from conventional diazo precursors, namely, they react with alkenes to give cyclopropanes and undergo insertion into C? H bonds of alkanes. In many cases the carbenes formed may also be detected by EPR and optical spectroscopic methods.     

Selective and facile synthesis of α,β-unsaturated nitriles and amides with N-hydroxyphthalimide as the nitrogen source

The direct conversion of α,β-unsaturated aldehydes to corresponding nitriles promoted by Pd(OAc)₂ and phthalic acid which was hydrolyzed from N-hydroxyphthalimide (NHPI) has been disclosed. Additionally, it was found that when water was used as the solvent, α,β-unsaturated amides was obtained as the main products in good to excellent yields. It was first reported that NHPI was utilized as the nitrogen source to synthesize α,β-unsaturated nitriles and amides from aldehydes. Control experiment demonstrated that aldehydes undergo a process of oximation and dehydration to form nitriles and amides.     

Highly chemoselective 2,4,5-triaryl-1,3-dioxolane formation from intermolecular 1,3-dipolar addition of carbonyl ylide with aryl aldehydes

[reaction: see text] Rhodium(II) acetate catalyzed 1,3-dipolar cycloaddition of methyl phenyldiazoacetate with a mixture of electron-rich and electron-deficient aryl aldehydes gave 1,3-dioxolanes in high yield with excellent chemoselectivity.     

Synthesis of α-hydroxy-γ-butyrolactones from acrylates and 1,3-dioxolanes using N-hydroxyphthalimide (NHPI) as a key catalyst

A new route to α-hydroxy-γ-butyrolactones through three-component radical coupling of 1,3-dioxoranes, acrylates, and molecular oxygen using N-hydroxyphthalimide (NHPI) as a key catalyst has been developed. For example, the addition of 1,3-dioxarane to methyl acrylate under dioxygen by NHPI followed by catalytic hydrogenation of the resulting adduct on Pd/C afforded α-hydroxy-γ-butyrolactone in good yield. This method provides a facile approach to α-hydroxy-γ-butyrolactones, which are difficult to synthesize by conventional methods.     

Aerobic oxidation of N-alkylamides catalyzed by N-hydroxyphthalimide under mild conditions. Polar and enthalpic effects

The oxidation of N-alkylamides by O(2), catalyzed by N-hydroxyphthalimide (NHPI) and Co(II) salt, leads under mild conditions to carbonyl derivatives (aldehydes, ketones, carboxylic acids, imides) whose distribution depends on the nature of the alkyl group and on the reaction conditions. Primary N-benzylamides lead to imides and aromatic aldehydes at room temperature without any appreciable amount of carboxylic acids, while under the same conditions nonbenzylic derivatives give carboxylic acids and imides with no trace of aldehydes, even at very low conversion. These results are explained through hydrogen abstraction by the phthalimide-N-oxyl (PINO) radical, whose reactivity with benzyl derivatives is governed by polar effects, so that benzylamides are much more reactive than the corresponding aldehydes. The enthalpic effect is, however, dominant with nonbenzylic amides, making the corresponding aldehydes much more reactive than the starting amides. The importance of the bond dissociation energy (BDE) of the O-H bond in NHPI is emphasized.     

Atmospheric oxidative catalyst-free cross-dehydrogenative coupling of aldehydes with N-hydroxyimides

Cross-dehydrogenative coupling (CDC) reactions of aldehydes with N-hydroxyimidates such as N-hydroxysuccinimide (NHSI), N-hydroxyphthalimide (NHPI) under catalyst-free conditions is described. Moreover, the desired products can be obtained simply by recrystallization from ethanol. This method is also applicable to the synthesis of amides in excellent yields. A radical mechanism of the type shown in Scheme 4 is proposed based upon the inhibition of the reaction in the presence of TEMPO.     

Indirect electrochemical α-methoxylation of aliphatic ethers and acetals - reactivity and regioselectivity of the anodic oxidation using tris(2,4-dibromophenyl)amine as redox catalyst

The technically important α-methoxylation of aliphatic ethers and acetals to form mixed acetals respectively aldehydes or ortho-esters can be performed electrochemically at low potentials in methanol solution using an undivided cell and tris(2,4-dibromophenyl)amine as redox catalyst. The regioselectivity is usually considerably higher as compared with direct electrolysis in the absence of a catalyst. Especially valuable is the method for the regioselective methoxylation of secondary carbon atoms in presence of primary or tertiary ones and of the acetal carbon in 1,3-dioxolanes. The redox catalyst is stable under the reaction conditions so that more than thousand turnovers could be obtained.     

An unexpected 1,2-hydride shift in phosphoric acid-promoted cyclodimerization of styrene oxides under solvent-free conditions. A synthetic route towards 2,4-disubstituted 1,3-dioxolanes

A 1,2-hydride shift in the phosphoric acid-promoted cyclodimerization of styrene oxide and its chloro derivatives under solvent-free conditions leading to 2,4-disubstituted 1,3-dioxolanes is described. Methoxy substituents on the aromatic ring of the styrene oxide prevent the 1,2-hydride shift reaction leading to substituted 1,4-dioxanes. A possible mechanism for the formation of the 1,3-dioxolanes is proposed.     

Copper(II) bromide as an efficient catalyst for acetal to bisarylmethyl ether interconversion

Transprotection of acetals to bis(methoxyphenyl)methyl (BMPM) ethers can be efficiently achieved in the presence of copper dibromide as catalyst in acetonitrile at room temperature. Acetals are conveniently and selectively converted to the corresponding mono-protected diol with bis(methoxyphenyl)methyl isopropyl ether (BMPMOiPr) as the reagent. This new practical reagent allows the BMPM transfer to 1,3-dioxolanes or 1,3-dioxanes under copper catalysis. The reaction conditions are also very mild and tolerant to various functional groups, including other protecting groups.