Synthesis of α,β-unsaturated ketone from α-iodo ketone using photoirradiation

Irradiation of α-iodo ketone in hexane under a nitrogen atmosphere with a high-pressure mercury lamp (λ>300nm) at room temperature afforded the corresponding α,β-unsaturated ketones in good yield. This reaction affords a new, clean and convenient synthetic method for the α,β-unsaturated ketone.     

Reactions of methylated cyclopropanes and olefins with chloroplatinic acid II. Monoacylation and the formation of β,γ-unsaturated carbonyl complexes of platinum dichloride

Upon reaction with chloroplatinic acid in acid anhydride solvents, several methyl-substituted cyclopropanes and olefins form platinum dichloride adducts of β,γ-unsaturated carbonyls in which the ligand is bound to platinum through both the olefin π-system and a lone pair on the carbonyl oxygen. The cyclopropane reactions are shown to proceed initial isomerization to an olefin, followed by acylation and proton loss. The stereochemistry of the products is shown to be dependent upon the substitution on the carbons α and β to the carbonyl, and in the case where both the α- and β-carbons are methyl-substituted a single conformation cf the product is isolated.     

The combination of 2-NsNH2/NCS and MeCN as the nitrogen sources for the regio- and stereoselective formation of imidazolines from α,β-unsaturated ketones

A new nitrogen source combination was found for the regio- and stereoselective diamination of α,β-unsaturated ketones. This combination employs the readily available and inexpensive combination of NCS and 2-NsNH₂ as the electrophilic nitrogen source, and acetonitrile as the nucleophilic nitrogen source, respectively. The reaction is easily performed by mixing olefin, 2-NsNH₂, NCS and 4 Å molecular sieves in freshly distilled acetonitrile at room temperature. The reaction is chemoselective without the formation of any haloamine side products. A new aziridinium ion formed from enones and 2-NsNHCl is suggested to exist and to react with nitrile via a [2+3] cycloaddition mechanism, which is responsible for the excellent regio-, stereoselectivity of the resulting diamination products.     

A novel method for the synthesis of (Z)-α-selenyl-α,β-unsaturated ketones via acylation of (E)-α-selanylvinylstannanes

The (E)-α-selenylvinylstannanes react with acyl halides in presence of a catalytic amount of Pd(PPh₃)₄ to give the corresponding (Z)-α-selenyl-α,β-unsaturated ketones in good yield.     

Potassium phosphate or silica sulfuric acid catalyzed conjugate addition of thiols to α,β-unsaturated ketones at room temperature under solvent-free conditions

Potassium phosphate and silica sulfuric acid have been found to be useful and highly efficient catalysts for conjugate addition of thiols to α,β-unsaturated ketones under solvent-free conditions, at room temperature. Silica sulfuric acid (SSA) was found to be suitable for electron-deficient enones while potassium phosphate was found to effect thia-Michael addition with both, electron-deficient as well as electron-rich conjugated ketones.     

[3+3] Cyclization reactions of β-nitroenamines and β-enaminonitriles with α,β-unsaturated carboxylic acid chlorides

New indolizidines, quinolizidines, and octahydro-pyrido[1,2-a]azepines of lactam type were synthesized from 2-nitromethylene-pyrrolidine, -piperidine, and -hexahydroazepine, respectively, by [3+3] cyclizations with α,β-unsaturated carboxylic acid chlorides. In the case of quinolizidines, a double bond migration was observed, and explained in terms of amidity percentage. Cyanomethylene-pyrrolidine gave indolizidines of lactam type, while transformations of 1-cyanomethylene-tetrahydoisoquinoline resulted in lactams as well as ketones, when simple open-chain acid chlorides or cinnamoyl chloride were used, respectively.     

Photochemie von tricyclischen β, γ-γ′, δ′-ungesättigten Ketonen. 50. Mitteilung über Photoreaktionen

Photochemistry of tricyclic β, γ-γ′, δ′-unsaturated ketones The easily available tricyclic ketone 1 (cf. Scheme 1) with a homotwistane skeleton yielded upon direct irradiation the cyclobutanone derivative 3 by a 1,3-acyl shift. Further irradiation converted 3 into the tricyclic hydrocarbon 4 . However, acetone sensitized irradiation of 1 gave the tetracyclic ketone 5 by an oxa-di-π-methane rearrangement. Again with acetone as a sensitizer the ketone 5 was quantitatively converted to the pentacyclic ketone 6 . The conversion 5 → 6 represents a novel photochemical 1,4-acyl shift. The possible mechanisms are discussed (see Scheme 7). The tricyclic ketone 2 underwent similar types of photoreactions as 1 (Scheme 2). Unlike 5 the tetracyclic ketone 9 did not undergo a photochemical 1,4-acyl shift. The epoxides 10 and 14 derived from the ketones 1 and 2 , respectively, underwent a 1,3-acyl shift upon irradiation followed by decarbonylation, and the oxa-di-π-methane rearrangement (Schemes 3 and 4). The diketone 18 derived from 1 behaved in the same way (Scheme 5). The tetracyclic diketone 21 cyclized very easily to the internal aldol product 22 under the influence of traces of base (Scheme 5). Upon irradiation the γ, δ-unsaturated ketone 24 underwent only the Norrish type I cleavage to yield the aldehyde 25 (Scheme 6).     

A simple method to prepare single isomer tetrasubstituted olefins by successive Suzuki–Miyaura cross-couplings of E-β-chloro-α-iodo-α,β-unsaturated esters

A convenient method of synthesizing tetrasubstituted olefins as single isomers is described. E-β-Chloro-α-iodo-α,β-unsaturated esters are first converted into the corresponding E-β-chloro-α,β-unsaturated esters using Suzuki–Miyaura coupling reactions with arylboronic acids and alkenylboronic acids. These transformations gave complete selectivity, and proceeded with substitution at the more activated α-iodide position. These compounds, isolated as single isomers, were then transformed into tetrasubstituted olefins by Suzuki–Miyaura couplings with arylboronic acids, alkenylboronic acids, and alkyl boranes to afford the corresponding tetrasubstituted olefins as single isomers. During this coupling process, it was discovered that the use of small ligands, such as PMe₃ or PEt₃, was critical for efficient coupling. The stereochemistry and regiochemistry of the products were unequivocally established using NMR methods.     

Regioselective SN′ allylic substitution versus 1,4-addition: Synthesis of α-substituted β,γ-unsaturated esters

The reaction of the higher order organocuprate reagents R₂Cu(CN)Li₂-BF₃ with γ-bromo α,β-unsaturated esters gives with very high selectivity α-substituted β,γ-unsaturated esters arising from a SN′ allylic substitution. This reaction allows an easy access to α-silyl β,γ-unsaturated esters.     

A novel synthesis of α-hydroxy- and α,α′-dihydroxyketone from α-iodo and α,α′-diiodo ketone using photoirradiation

A novel reaction of α-iodo ketone (α-iodocycloalkanone, α-iodo-β-alkoxy ester, and α-iodoacyclicketone) with irradiation under a high-pressure mercury lamp gave the corresponding α-hydroxyketone in good yields. In the case of α,α′-diiodo ketone, α,α′-dihydroxyketone which little has been reported until now was obtained. This reaction affords a new, clean and convenient synthetic method for α-hydroxy- and α,α′-dihydroxyketone.     

Microwave-assisted synthesis of α-hydroxy ketone and α-diketone and pyrazine derivatives from α-halo and α,α′-dibromo ketone

A novel reaction of α-halo ketone (α-bromo and α-chloro ketone) with irradiation under microwave gave the corresponding α-hydroxyketone and pyrazine derivative in good yields. In the case of α,α′-dibromo ketone, α-diketone was obtained. This reaction affords a new, clean and convenient synthetic method for α-hydroxyketone, α-diketone, α-chloro ketone and pyrazine derivative.     

Synthesis of α,β-unsaturated oxathiolanes

The formation of α,β-unsaturated oxathiolanes 2 from α,β-unsaturated carbonyl derivatives was achieved selectively and in high yields using the heterogeneous catalyst APSG·HCl.     

Diaryl-2-pyrrolidinemethanols catalyzed enantioselective epoxidation of α,β-enones: new insight into the effect of structural modification of the catalyst on reaction efficiency

Catalytic enantioselective epoxidation of α,β-unsaturated ketones promoted by diaryl-2-pyrrolidinemethanols and tert-butyl hydroperoxide (TBHP) is described. Investigation on structural modifications of the diaryl-2-pyrrolidinemethanols showed that fine tuning of the stereoelectronics of the substituents on the aryl moiety is important to achieve high efficiency. By employing a structurally optimized organocatalyst, significantly reduced loading (10 mol %) can be used to produce the epoxides in high yield and up to 90% ee at room temperature.     

Spectral correlations for β-chlorovinyl ketones

The IR and UV spectroscopic data of a series of alkyl substituted β-chlorovinyl ketones have been determined. Some of the IR and UV spectroscopic criteria, developed for the S-cis or S-trans conformation of ordinary α,β-unsaturated ketones, seem to be applicable for the β-chlorovinyl ketones: the S-cis conformer shows a low ratio (rⁱ) of the integrated intensities of the carbonyl and double bond stretching vibrations and a relatively low UV ε value; whereas high rⁱ and ε values are found for the S-trans conformer; non-planarity increases the rⁱ value and decreases the ε value.The prefered conformations as determined by the IR and UV spectral data have led to the presentation of benzene solvation models for a series of β-chlorovinyl ketones. These models made it possible to assign thecis ortrans structure to α,β-dialkyl-β-chlorovinyl ketones on the basis of the NMR aromatic solvent induced shifts of the β-alkyl group: high solvent shifts to a higher field (0·31–0·66 ppm) are found forcis-β-chlorovinyl ketones, whereas low solvent shifts (0·040·15) are found for thetrans-β-chlorovinyl ketones. Assignments based on the chemical shifts alone can lead to erroneous interpretations.     

Evidence for an enolate mechanism in the asymmetric Michael reaction of α,β-unsaturated aldehydes and ketones via a hybrid system of two secondary amine catalysts

The key nucleophile was found to be neither an enamine nor an enol, but an enolate in the direct Michael reaction of α,β-unsaturated aldehydes and non-activated ketones catalyzed by two amine catalysts namely diphenylprolinol silyl ether and pyrrolidine. This is a rare example of an enolate from a ketone serving as a key intermediate in the asymmetric organocatalytic reaction involving secondary amine catalysts because the ketone enolates are generally generated using a strong base, and the enamine is a common nucleophile in this type of reaction.

The key nucleophile was found to be neither an enamine nor an enol, but an enolate in the direct Michael reaction of α,β-unsaturated aldehydes and non-activated ketones catalyzed by two amine catalysts namely diphenylprolinol silyl ether and pyrrolidine.     

Dual-activation protocol for tandem cross-aldol condensation: An easy and highly efficient synthesis of α,α′-bis(aryl/alkylmethylidene)ketones

Commercially available lithium hydroxide monohydrate (LiOH·H₂O) was found to be a novel ‘dual activation’ catalyst for tandem cross-aldol condensation between cyclic/acyclic ketones and aromatic/heteroaromatic/styryl/alkyl aldehydes leading to an efficient and easy synthesis of α,α′-bis(aryl/alkylmethylidene)ketones at r.t. in short times. The reaction of aryl, heteroaryl, styryl and alkyl aldehydes with acyclic and five/six-membered cyclic ketones afforded excellent yields after 2 min to 1.25 h. The reaction conditions were compatible with various electron withdrawing and electron donating substituents, e.g. Cl, F, NO₂, OMe and NMe₂. The rate of the cross-aldol condensation was influenced by the nature of the ketone and electronic and steric factors associated with the aldehyde. The reaction took place at a faster rate for acyclic ketone (e.g., acetone) than that for cyclic ketone (e.g., cyclohexanone). In case of cycloalkanones, the rate of the reaction was dependent on the size of the ring of the cycloalkanone. The cross-aldol condensation of cyclopentanone was faster than that of cyclohexanone for a common aldehyde. In case of reactions involving aliphatic aldehyde having α-hydrogen atom no self-aldol condensation of the aldehyde took place.     

Addition of trimethylsilylmethylmagnesium chloride to α, β-unsaturated carbonyls

Reactions of α,β-unsaturated carbonyl compounds with Me₃SiCH₂MgCl, prepared from chloromethyltrimethylsilane [1], were examined. Unlike its lithium counterpart (Me₃SiCH₂Li), which adds to α,β-unsaturatedketones in the 1,2-sense, the Grignard reagent afforts γ silanes via a 1,4-addition sequence. This tendency is accentuated by the addition of Cu₂Br₂. Addition of the Grignard reagent to α,β-unsaturated aldehydes gives the simple 1,2-addition products.     

An evaluation of the Noyori system “in reverse”: Thermodynamic and kinetic parameters of secondary alcohol transfer dehydrogenation catalyzed by [(η-1-Pr-4-Me-C6H4)Ru(HN-CR′R″-CR′R″NTs)], R′ = H, Me; Ph, R″ = H, Me

The 16 electron ruthenium complexes [(η⁶-1-isopropyl-4-methyl-benzene)(X-N)Ru(II)], where X-N is 2-amido-1-ethoxide (2), 1-N-p-tosyl-1,2-diamido-ethane (3), 1-N-p-tosyl-1,2-diamido-benzene (7), 1-N-(p-tosyl)-1,2-diamido-1,1,2,2-tetramethyl-ethane (8) and 1-N-(p-tosyl)-1,2-diamido-meso-1,2-diphenyl-ethane (9) have been evaluated as catalysts for the transfer dehydrogenation of secondary alcohols to ketones in acetone and/or cyclohexanone solvent. Complexes 2 and 3 cannot be isolated and decompose under these conditions. In contrast complexes 7, 8 and 9 are supported by ligands designed to resist β-hydride elimination and can with the exclusion of oxygen be held in solution for weeks. Complex 7 is not active as a catalyst. Complexes 8 and 9 are highly air-sensitive and active as catalysts for transfer (de)hydrogenations under oxidizing and reducing conditions, respectively. There is no coordinative inhibition of the catalysts by the ketone solvent under oxidizing conditions, but both catalysts show a correlation between the reaction rates and the ΔG values of the reactions with reactions leading to α, β-unsaturated ketones proceeding faster. For all alcohol/ketone substrate pairs where the ketone is not α, β-unsaturated, the hydrogenation reactions under reducing conditions (iso-propanol solvent) are at least one order of magnitude faster than the corresponding dehydrogenation reaction under oxidizing conditions (acetone solvent).     

Synthese stereoselective d'esters α,β- ethyleniques α-methyles Z ou E par la reaction de wittig-horner a partir de phosphonates ou d'oxydes de phosphine

The reaction of α-branched aldehydes with diethyl 1-carbomethoxyethyl phosphonate 1b in THF/nBuLi at low temperature leads stereoselectively to Z α-methyl α,β-unsaturated esters. From a linear aldehyde, the reaction is less stereoselective, while from α,β-unsaturated ones, the E isomers are predominantly formed in good yields. From diphenyl 1-carbomethoxyethyl phosphine oxide 2b, E α-methyl α,β-unsaturated esters are stereoselectively formed either in DMF/tBuOK or in phase transfer conditions, whatever the starting aldehyde is, also in good yields. This reagent can thus advantageously replace the corresponding P-ylid. In all cases, the reaction conditions are determined so that by-products formation is minimized.     

A New α,β-Enone → Alkynone Fragmentation. Syntheses of exaltone® and (±)-muscone

p-Toluenesulfonylhydrazones of α, β-unsaturated ketones undergo an alkynone fragmentation in high yield when treated with electrophiles under basic conditions. With N -bromosuccinimide in alcohols, the p-tosylhydrazones 4a and 4b yielded in a one-pot reaction the cyclic 4-alkyn-1-ones 5a and 5b ; these were converted to Exaltone® ( 1a ) and muscone ( 1b ) on catalytic hydrogenation.