Diaryl-substituted ketones

Diarylation of ketones 1-23 Ring closure of aryl-substituted carbonyl compounds... 

High yields of monoaryl- or diaryl-substituted difluoromethanes can be achieved by reacting the corresponding dilhiolanes with nilrosonium tetralluoroborate and hydrogen fluoride/ pyridine.Dialkyldithiolanes undergo oxidative cleavage to (he parent ketones. 

Conjugated yne-2-ynylidene 1,3-dithioles 228 were synthesized via Wittig reactions of phosphonium salts 225 with 3-phenyl-substituted propargyl aldehydes 227 (R = H, = Ph). Diaryl-substituted derivatives 228 were prepared in Horner-Wittig reactions of phosphonates 226 with ketones 225 (R =R = Ph or -02NC6H4) (Equation 13) <2004CL1190>. 

An alternative tandem Michael addition/aldol condensation for the synthesis of 3,5-diaryl-substituted phenols 121 employs, instead of 1-(2-oxopropyl)pyridinium chloride (112), l-(benzotriazol-l-yl)propan-2-one (119) in the presence of excess of NaOH in refluxing ethanol (equation 106) ". Under these conditions, several types of 3,5-diaryl-substituted phenols 121 have been obtained in 52-94% yield. The reaction proceeds by Michael addition of the enolate of 119 to the a,/3-unsaturated ketone 118 to afford intermediate 120, which then undergoes an intramolecular aldol condensation with elimination of benzotriazole. 

A particularly difficult situation arises when combining in the same reaction the use of these rather unreactive acceptors such as enones with the incorporation of ketones as Michael donors in which the formation of the intermediate enamine by condensation with the amine catalyst is much more difficult. For this reason, the organocatalytic Michael addition of ketones to enones still remains rather unexplored. An example has been outlined in Scheme 2.22, in which it has been shown that pyrrolidine-sulfonamide 3a could catalyze the Michael reaction between cyclic ketones and enones with remarkably good results, although the reaction scope was exclusively studied for the case of cyclic six-membered ring ketones as nucleophiles and 1,4-diaryl substituted enones as electrophiles. In this system the authors also pointed toward a mechanism involving exclusively enamine-type activation of the nucleophile, with no contribution of any intermediate iminium species which could eventually activate the electrophile. Surprisingly, the use of primary amines as catalysts in this transformation has not been already considered. 

Harikrishna and collaborators devised an iodine-promoted oxidative transformation of o-vinyl diaryl ketones into o-acetyl diaryl ketones, which then were used to prepare l-methyl-4-arylphthalazines 16 (Scheme 10) (14EJO1066). The ori/io-vinyl-substituted ketones were obtained in moderate-to-good yields via treatment ofWeinreb amide 17 with either... 

Transition metals can be eliminated from the catalytic systems. Thus, a quinine-derived urea organocatalyst is effective in the enantioselective oxidation of a wide range of diaryl-substituted meso-1,2-diols using bromi-nation reagents as oxidants (Scheme 31). " The method is simple, operates at ambient temperature and utilizes available reagents to yield a-hydroxy ketones in good yields (up to 94%) and enantioselectivities (up to 95% ee). 

Isolated carbonyls always give epoxides from the Corey-Chaykovsky reaction. Take the aldehyde substrate as an example. Spiro epoxide 30 was produced from the reaction of trisnorsqualene aldehyde 28 (R20 represents the polyene side-chain with 20 carbons) with substituted sulfur ylide 29, prepared in situ from cyclopropyldiphenylsulfonium tetrafluoroborate and KOH. " For the epoxidation of ketones, the Corey-Chaykovsky reaction works well for diaryl- (31), arylalkyl- (32), ... 

Ordinary ketones are generally much more difficult to cleave than trihalo ketones or p-diketones, because the carbanion intermediates in these cases are more stable than simple carbanions. However, nonenolizable ketones can be cleaved by treatment with a 10 3 mixture of t-BuOK—H2O in an aprotic solvent such as ether, dimethyl sulfoxide, 1,2-dimethoxyethane (glyme), and so on, or with sohd t-BuOK in the absence of a solvent. When the reaction is applied to monosubstituted diaryl ketones, that aryl group preferentially cleaves that comes off as the more stable carbanion, except that aryl groups substituted in the ortho position are more readily cleaved than otherwise because of the steric effect (relief of stain). In certain cases, cyclic ketones can be cleaved by base treatment, even if they are enolizable. " OS VI, 625. See also OS VH, 297. 

The easiest substrates to test are acetophenones, as many substituted analogues are commercially available from laboratory suppliers. A large range of results have been reported the best enantiomeric excesses achieved and relevant literature reference are detailed in Tables 35.4 and 35.5. The range of ketones that can be reduced includes substituted diaryl, dialkyl and arylalkyl ketones, alpha-,... 

A synthesis of A-substituted a-aminobenzylphosphinic acids starts from ammonium hypophosphite this is allowed to react with primary amines together with aldehydes or ketones in the presence of HC1.60 The nature of the products and general success of the Atherton-Todd reaction for the preparation of dialkyl- and diaryl-phosphinic amides from secondary phosphine oxides depends on the order in which reactants are mixed and on the choice of polyhalogen reactant.61... 

A large number of diaryl ketone substrates, including those listed in Table 9.3, have been reduced with high enantioselectivity with the protocol described here. Unlike analogous chemical catalysts, the commercially available biocatalysts displayed no dependence on ortho substitutions or electronic dissymmetry, and produced diaryl methanols with good to excellent ee values in nearly all cases. 

Lack of reactivity in some 0-substituted diaryl ketones in spite of their Tj (n, state has been found to be due to the possibility of intramolecular H-abstraction... 

The lower members of the homologous series of 1. Alcohols 2. Aldehydes 3. Ketones 4. Acids 5. Esters 6. Phenols 7. Anhydrides 8. Amines 9. Nitriles 10. Polyhydroxy phenols 1. Polybasic acids and hydro-oxy acids. 2. Glycols, poly-hydric alcohols, polyhydroxy aldehydes and ketones (sugars) 3. Some amides, ammo acids, di-and polyamino compounds, amino alcohols 4. Sulphonic acids 5. Sulphinic acids 6. Salts 1. Acids 2. Phenols 3. Imides 4. Some primary and secondary nitro compounds oximes 5. Mercaptans and thiophenols 6. Sulphonic acids, sulphinic acids, sulphuric acids, and sul-phonamides 7. Some diketones and (3-keto esters 1. Primary amines 2. Secondary aliphatic and aryl-alkyl amines 3. Aliphatic and some aryl-alkyl tertiary amines 4. Hydrazines 1. Unsaturated hydrocarbons 2. Some poly-alkylated aromatic hydrocarbons 3. Alcohols 4. Aldehydes 5. Ketones 6. Esters 7. Anhydrides 8. Ethers and acetals 9. Lactones 10. Acyl halides 1. Saturated aliphatic hydrocarbons Cyclic paraffin hydrocarbons 3. Aromatic hydrocarbons 4. Halogen derivatives of 1, 2 and 3 5. Diaryl ethers 1. Nitro compounds (tertiary) 2. Amides and derivatives of aldehydes and ketones 3. Nitriles 4. Negatively substituted amines 5. Nitroso, azo, hy-drazo, and other intermediate reduction products of nitro com-pounds 6. Sulphones, sul-phonamides of secondary amines, sulphides, sulphates and other Sulphur compounds... 

Alkyl- or aryl-dibenzothiophenes are conveniently prepared from the 2-arylthio-cyclohexanones, which are readily cyclized and dehydrogenated to yield the respective 1-, 2-, 3- or 4-substituted dibenzothiophenes (382 equation 9 Section 3.15.2.3.2). More complex polycyclic systems are available, using suitable aryenethiols, such as naph-thalenethiols, and 2-bromo-l-tetralone to synthesize the appropriate 2-arylthio ketones. Diaryl sulfides can be converted to dibenzothiophene derivatives in satisfactory yields by photolysis in the presence of iodine (equation 10) (75S532). Several alkyldibenzothiophenes with substituents in the 2- and/or 3-positions were prepared in satisfactory yield by the condensation of dichloromethyl methyl ether with substituted allylbenzo[6]thiophenes (equation 11) (74JCS(P1)1744). 

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