Direct organocatalytic asymmetric α-oxidation of ketones with iodosobenzene and N-sulfonyloxaziridines

The novel, direct amino acid-catalyzed α-oxidation of ketones with iodosobenzene and N-sulfonyloxaziridines is presented. A screen of several synthetically common oxidants revealed that iodosobenzene and N-sulfonyloxaziridines act as electrophiles in the direct organocatalytic asymmetric α-hydroxylation of ketones. The direct proline-catalyzed asymmetric α-oxidation of ketones with iodosobenzene yielded the corresponding α-hydroxylated ketones with up to 77% ee. Furthermore, several amino acid derivatives catalyze the stereoselective α-oxidation of ketones with N-sulfonyloxaziridines. For example, the direct diamine-catalyzed enantioselective α-hydroxylation of ketones with N-sulfonyloxaziridines furnished the corresponding α-hydroxylated products in moderate yield with up to 63% ee.     

Practical one-pot preparation of ketones from aryl and alkyl bromides with aldehydes and DIH via Grignard reagents

Various diaryl ketones, alkyl aryl ketones, and dialkyl ketones were efficiently prepared in good yields by the reactions of the Grignard reagents derived from aryl or alkyl bromides, followed by the reactions with aromatic or aliphatic aldehydes and the subsequent treatment with 1,3-diiodo-5,5-dimethylhydantoin and K₂CO₃, in a one-pot method. The same treatment of aromatic bromides bearing electron-withdrawing groups, such as ester, nitrile, ketone, and nitro groups with i-PrMgCl·LiCl or PhMgCl instead of Mg, also provided the corresponding diaryl and alkyl aryl ketones in good yields. The above methods are simple and practical transition-metal-free methods for the preparation of various diaryl ketones and alkyl aryl ketones bearing electron-rich aromatic groups and electron-deficient aromatic groups, as well as dialkyl ketones.     

1,2-联烯基酮的合成与反应

1,2-联烯基酮可以通过2-丙炔基酮异构化反应,相应有机金属试剂中间体与酯、酰氯或酰胺的反应,[2,3]或[3,3]迁移反应,Wittig反应,消除反应,2,3-联烯醇氧化等方法合成。由于联烯酮上含有吸电子基团羰基,它可发生亲核加成、环加成、环化反应。     

Catalytic ketone olefination with methyltrioxorhenium

Methyltrioxorhenium (MTO) catalyses the olefination of ketones with ethyl diazoacetate in the presence of triphenylphosphane. Unactivated ketones require the addition of 0.5 equiv of benzoic acid to achieve good yields, while trifluoromethyl ketones require no co-catalyst. The optimised system allows the olefination of aromatic, aliphatic, unsaturated, cyclic and trifluoromethyl ketones.     

Reduction of Aromatic α-Halo Ketones with Metallic Bismuth

Aromatic α-bromo ketones and α-iodio ketones can be reduced by bismuth prepared from NaBH₄ and BiCl₃ in water to their parent ketones in high yields, but aromatic α-chloro ketones should be added to sodium iodide first.     

New synthetic routes towards various α-fluorinated aryl ketones and their enantioselective reductions using baker's yeast

Highly electrophilic dichlorofluoromethyl aryl ketones were obtained by oxidation of dichlorofluoromethyl aryl alcohols. Subsequent dechlorination of these ketones using sodium formaldehyde sulfoxylate (Rongalite) and reductive dehalogenating system SnCl₂/Al led to various fluoromethyl aryl ketones and chlorofluoromethyl aryl ketones, respectively. Asymmetric reductions of these fluorinated ketones using the inexpensive baker's yeast produced the corresponding fluoromethyl aryl alcohols with different enantioselectivities.     

Mn(III)-based C-C bond formation: regioselective α′-allylation of various α,β-unsaturated, α and β-alkoxy α,β-unsaturated ketones

The Manganese(III)-based regioselective α′-keto radical generation of unsaturated ketones is a versatile synthetic procedure with broad applicability. The generated α′-keto radical slowly creates a metal enolate in a solvent at reflux. The resultant metal enolate affords the corresponding α′-allylated α,β-unsaturated ketones in good yields. This method is the first example of the metal mediated regioselective α′-allylation of α,β-unsaturated ketones. The ketones that have α or β-alkoxy groups also work efficiently.     

A novel photoinduced ring opening and isomerization of adamantane-2-spiro isoxazolines using Mo(CO)6

The Mo(CO)₆-mediated photoinduced ring-opening reactions of adamantane isoxazolines involve novel rearrangement that provide enaminoketones as major products and β-hydroxy ketones as minor ones; in contrast, only β-hydroxy ketones and α,β-unsaturated ketones were obtained under thermal condition.     

Chiral [RuCl2(dipyridylphosphane)(1,2‐diamine)] Catalysts: Applications in Asymmetric Hydrogenation of a Wide Range of Simple Ketones

The dipyridylphosphane/diamine–Ru complex combined with tBuOK in 2propanol acts as a very effective catalyst system for the enantioselective hydrogenation of a diverse range of simple ketones including heteroaromatic ketones, substituted benzophenones, alkenyl ketones, and cyclopropyl ketones. The combination of desirable features, such as quantitative chemical yields within hours, broad substrate scope, excellent enantioselectivities (up to 99 %), and high substrate‐to‐catalyst ratios, among others, makes the present catalyst system of high practical interest.     

Synthesis and Rhizopus oryzae mediated enantioselective hydrolysis of α-acetoxy aryl alkyl ketones

Mn(OAc)₃ oxidation of aromatic ketones afforded the α-acetoxy ketones in good yield. Selective hydrolysis of the acetoxy ketones by the fungus Rhizopus oryzae yields (R)-hydroxy ketones in high enantiomeric excess.     

Studies on K2CO3-catalyzed 1,4-addition of 1,2-allenic ketones with diethyl malonate: controlled selective synthesis of beta,gamma-unsaturated enones and alpha-pyrones

The K2CO3 (10 mol %)-catalyzed 1,4-addition reaction of diethyl malonate with various substituted 1,2-allenic ketones leading to polyfunctionalized beta,gamma-unsaturated enones 3 or 4 was studied. With 3-unsubstituted 1-substituted-1,2-allenyl ketones, the highly selective formation of beta,gamma-unsaturated enones 4 was observed; with 1,2-allenyl ketones bearing one or two 3-substituents in the allenyl group, only beta,gamma-unsaturated enones 3 with an unmigrated carbon-carbon double bond were produced; with 3-monosubstituted-1,2-allenyl ketones Z-beta,gamma-unsaturated enones 3 were formed with excellent stereoselectivity (E:Z > 96:4); with propadienyl ketones, mixtures of beta,gamma-unsaturated enones 3 and 4 were formed. alpha-Pyrone derivatives were synthesized via the K(2)CO(3)-catalyzed or -promoted reaction of 1,2-allenic ketones with diethyl malonate via a sequential Michael addition-carbon-carbon double bond migration-lactonization process.     

Microwave-assisted synthesis of α-hydroxy aromatic ketones from α-bromo aromatic ketones in water

A reaction ofα-bromo aromatic ketones in water with microwave irradiation gave the correspondingα-hydroxy aromatic ketones in good yields.The use of microwaves was found to significantly improve yields and shorten the reaction time.This reaction afforded a very clean,convenient method for the synthesis ofα-hydroxy aromatic ketones.     

Chemische Verschiebungen bei 17O-NMR. und Hydratations geschwindigkeiten von cyclischen Ketonen mit transannularer Wechselwirkung

In 8- and 9-membered cyclic ketones, transannular interactions of an EtN group or an O atom shift considerably the ¹⁷O signal of the carbonyl group to higher fields; S appears to have no such effect. The same ketones show markedly diminished speeds of water addition, compared to simple ketones; this reaction was followed by measuring the rate of oxygen exchange between ¹⁷O-labelled ketones and (unenriched) water. Transannular interaction inhibits completely in N-ethyl-azacyclodecane-6-one the exchange reaction, including labelling attemps.     

Facile Access to Sterically Hindered Aryl Ketones via Carbonylative Cross-Coupling: Application to the Total Synthesis of Luteolin

A general and mild protocol for achieving the carbonylative cross-coupling of sterically hindered, ortho-disubstituted aryl ketones is reported. The commercially available PEPPSI-IPr catalyst is shown to efficiently promote the carbonylative cross-coupling of hindered ortho-disubstituted aryl iodides to give diaryl ketones; traditional phosphine catalysts are less effective. Carbonylative Suzuki-Miyaura cross-couplings provide a diverse array of biaryl ketones in good to excellent yields. The same catalyst is also shown to catalyze a carbonylative Negishi cross-coupling reaction, utilizing a variety of alkynyl-zinc reagents to give the corresponding alkynyl aryl ketones. Application of this new methodology to the synthesis of the natural product luteolin is reported.     

Easy α-alkylation of ketones with alcohols through a hydrogen autotransfer process catalyzed by RuCl2(DMSO)4

The electrophilic α-alkylation of ketones with alcohols is accomplished by a hydrogen autotransfer process catalyzed by RuCl₂(DMSO)₄. The reaction can produce either simple alkylated ketones or α,β-unsaturated ketones just by choosing the appropriate starting ketones (methyl ketones or bicyclic methylenic ketones, respectively), as well as quinolines (by using 2-aminobenzyl alcohol derivatives) or the corresponding alcohol derivatives by the addition of an extra equivalent of the initial alcohol. In the last case, after the above alkylation process reduction of the carbonyl compound takes place. A mechanistic study seems to indicate that the process goes through the oxidation of the alcohols with ruthenium (after a previous deprotonation) to yield the corresponding aldehyde and a ruthenium hydride intermediate. In turn, the aldehyde suffers a classical aldol reaction with the starting ketone to form the corresponding α,β-unsaturated ketone, which finally is reduced through a Michael-type addition by the aforementioned ruthenium hydride intermediate.     

Synthesis of dibromo ketones by the reaction of the environmentally benign H<Subscript>2</Subscript>O<Subscript>2</Subscript>-HBr system with oximes

It was found that oximes undergo deoximation in the presence of the H₂O_2aq-HBr_aq system to form ketones and bromo ketones. This reaction provided the basis for the synthesis of dibromo ketones in yields varying from 40% to 94%. This method is environmentally friendly, sustainable, and easy to perform. The results of this investigation extend the potential of the use of oximes for the protection of carbonyl group, thus offering the ability to perform not only conventional deoximation but also the subsequent bromination of ketones. The reaction is easily scaled up and dibromo ketones can be prepared in gram amounts.      

The boron-mediated ketone-ketone aldol reaction

The first examples of the directed, boron-mediated aldol reaction between different ketones are presented. Transformation of a variety of ketones to their corresponding boron enolates with Chx₂BCl/Et₃N, followed by reaction with acceptor ketones in diethyl ether, and oxidation of the resultant boron aldolate (H₂O₂, MeOH/pH 7 buffer), provided the aldol addition products. The reaction was most facile when cyclic ketones were used, with the highest yields obtained for the reaction of boron enolates with cyclohexanone as the acceptor.     

Bi(OTf)3-catalyed One-pot Synthesis of α-Halo-β-amino Ketones and Acyl Aziridines from 3-Aryl Propargyl Alcohols

A Bi(OTf)₃-catalyed reaction of 3-aryl propargyl alcohols with sulfonamide and halogen source was firstly investigated, which provided a facile route for the synthesis of a large variety of α-halo-β-amino ketones. The key intermediates, β-amino ketones, were obtained through tandem Meyer-Schuster rearrangement reaction of propargyl alcohols and intermolecular Michael addition of α, β-unsaturated ketones and sulfonamide. Then the in situ generated α-halo-β-amino ketones underwent the base-promoted intramolecular cyclization to give diverse acyl aziridines in a one-pot fashion. These transformations are reliable on a large scale. The high yields and convenient experimental operations make it a valuable method for the construction of α-halo-β-amino ketones and acyl aziridine derivatives.     

Rhodium-catalyzed α-methylthiolation reaction of unactivated ketones using 1,2-diphenyl-2-methylthio-1-ethanone for the methylthio transfer reagent

In the presence of catalytic amounts of RhH(PPh₃)₄, 1,2-bis(diphenylphosphino)ethane (dppe), and dimethyl disulfide, ketones without α-activating groups were α-methylthiolated with 1,2-diphenyl-2-methylthio-1-ethanone giving α-methylthio ketones. The reaction of unsymmetrical ketones proceeded at the more substituted carbons. The initial formation of kinetic α-methylthiolated products followed by their rearrangement to thermodynamic products was observed in the reaction of α-phenyl ketones. Aldehydes, phenylacetate, and phenylacetonitrile were also α-methylthiolated under these conditions.     

Facile preparation of aromatic ketones from aromatic bromides and arenes with aldehydes

Aromatic ketones were efficiently prepared in good yields by the reactions of aryl bromides with n-BuLi, followed by the reactions with aromatic aldehydes or aliphatic aldehydes and the subsequent treatment with molecular iodine and K₂CO₃, in a one-pot method. The same treatment of arenes, instead of aromatic bromides, also provided the corresponding aromatic ketones in good yields. Using these methods, various diaryl ketones and alkyl aryl ketones bearing electron-rich aromatics and electron-deficient aromatics could be prepared efficiently by a simple, transition-metal-free, and therefore environmentally benign experimental procedure.