Cyclic ketones 2-arylated

Barluenga and coworkers first employed tosylhydrazones for Pd-catalyzed coupling reaction of aryl halides in the presence of bases (Fig. 4) [87]. The reaction is catalyzed by Pd2(dba)3 with Xphos as ligand. The tosylhydrazones can be those derived from cyclic ketones, aryl ketones, or alky carboxyaldehydes. Aryl chlorides or bromides... 

Aryl halides with a halogen activated by electron-withdrawing groups react with pyrrolidine enamines of cyclic ketones (68) to give the a-arylated ketones after hydrolysis. The enamine (28) with 2,4-dinitrochlorobenzene gave an excellent yield of 2(2,4-dinitrophenyl)cyclohexanone (88). The... 

Until this work, the reactions between the benzyl sulfonium ylide and ketones to give trisubstituted epoxides had not previously been used in asymmetric sulfur ylide-mediated epoxidation. It was found that good selectivities were obtained with cyclic ketones (Entry 6), but lower diastereo- and enantioselectivities resulted with acyclic ketones (Entries 7 and 8), which still remain challenging substrates for sulfur ylide-mediated epoxidation. In addition they showed that aryl-vinyl epoxides could also be synthesized with the aid of a,P-unsaturated sulfonium salts lOa-b (Scheme 1.4). 

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. 

Either or both of the R groups may be aryl. In general, dialkyl ketones and cyclic ketones react more rapidly than alkyl aryl ketones, and these more rapidly than diaryl ketones. The latter require sulfuric acid and do not react in concentrated HCl, which is strong enough for dialkyl ketones. Dialkyl and cyclic ketones react sufficiently faster than diaryl or aryl alkyl ketones or carboxylic acids or alcohols that these functions may be present in the same molecule without interference. Cyclic ketones give lactams. 

With alkyl aryl ketones, it is the aryl group that generally migrates to the nitrogen, except when the alkyl group is bulky. The reaction has been applied to a few aldehydes, but rarely. With aldehydes the product is usually the nitrile (16-21). Even with ketones, conversion to the nitrile is often a side reaction, especially with the type of ketone that gives 17-31. A useful variation of the Schmidt reaction treats a cyclic ketone with an alkyl azide (RN3) in the presence of TiCU, generating a... 

Bolm et al. (130) reported the asymmetric Baeyer-Villiger reaction catalyzed by Cu(II) complexes. Aerobic oxidation of racemic cyclic ketones in the presence of pivalaldehyde effects a kinetic resolution to afford lactones in moderate enan-tioselectivity. Aryloxide oxazolines are the most effective ligands among those examined. Sterically demanding substituents ortho to the phenoxide are necessary for high yields. Several neutral bis(oxazolines) provide poor selectivities and yields in this reaction. Cycloheptanones and cyclohexanones lacking an aryl group on the a carbon do not react under these conditions. 

In reactions which have some analogy with the interaction of dichloro-carbene/trichloromethyl anions with ketones, 2-dichloromethyloxazolines yield chloro-oxiranes and a-chlorocarbonyl compounds (Scheme 7.18). The formation of the oxiranes is favoured with aldehydes and lower homologue ketones, whereas cyclic ketones and aryl ketones are converted preferentially into the a-chloro carbonyl derivatives [18]. 

Later in 2007, Gong utilized If and saturated derivative 2 in a direct Mannich reaction between in situ generated N-aryl imines and cyclic ketones as well aromatic ketones (Scheme 5.3) [10], It was found that electron poor anilines as coupling partners gave the highest enantioselectivities. The authors postulate that acid promoted enolization of the ketone forms the reactive enol which adds to the protonated aldimine. 

Chiral sulfinimines 236 are very useful intermediates for the preparation of enantiomer-ically pure primary amines 237 (equation 158) . This reaction has been applied to the synthesis of a-amino acids . For sulfinimines obtained from simple ketones, lithium reagents are preferable for the addition , while for cyclic ketones organomagnesium compounds gave the best results. Addition of alkyl and aryl Grignard compounds to sulfinimines, derived from 3- and 4-substituted cyclohexanones, proceeds with excellent diastereoselectivity, depending on the stereochemistry of the ring substituents rather than the sulfinyl group . 

Either or both of the R groups may be aryl. In general, dialkyl ketones and cyclic ketones react more rapidly than alkyl aryl ketones, and these more rapidly than diaryl ketones. The... 

Oxidation of enamines.1 Oxidation of enamines of cyclic ketones in the presence of BFj etherate results in a Favorski type rearrangement to esters of contracted cycloalkanoic acids. A related reaction also occurs with enamines of aryl methyl ketones. 

Among the uses of other amino acids, L-tryptophan gives high ees and des in direct aldols of cyclic ketones and benzaldehydes in water 118 hydrophobic and aryl-stacking effects have been considered in explaining the selectivities. 

Arylations with aryliodonium salts can be effectively catalyzed by transition metals. The arylation of the lithium enolates of cyclic ketones with di-phenyliodonium triflate in the presence of stoichiometric quantities of copper cyanide affords the corresponding a-phenylated ketones in moderate yields [73]. 

Crafts reaction.4 This chapter presents a discussion of these methods and the various problems involved in the formation of cyclic ketones by the ring closure of aryl-substituted aliphatic acids.4 ... 

Remarkably, thermolysis of the Baylis-Hillman adducts 311 (R1 = alkyl or aryl Rz = Ac, CN, CC Me) in toluene at 210 °C in a sealed tube gave stereoselectively the cyclized product (+)-312, which included incorporation of the elements of the solvent and, when Rz = Ac, a single isomer was obtained (Equation 33). The yields were moderate (37-56%) and when RZ = CN and C02Me some racemization occurred. Similar results were obtained when either p-xylene or mesitylene was used but no reaction occurred when chlorobenzene or anisole was used. Unsaturated rings are obtained in similar yields and stereoselectivity if the N-substituent is an alkyne. In addition, benzene thiol reacted in boiling benzene in the presence of AIBN to give 313, which on ozonolysis yielded the cyclic ketones 314 ( = 1-3) in 52-70% yield <2001JOC1612>. 

The present review covers all the available published data on the Pfitzinger reaction beginning from the time of its discovery. The investigated material has been classified on the basis of the structure of the initial ketones separate sections cover the reactions of isatins with dialkyl ketones, keto acids, alkyl aryl ketones, and alkyl hetaryl ketones and also with cyclic ketones. Papers describing the synthesis of 4-quinolinecarboxylic acids by methods related to the Pfitzinger reaction are discussed in a separated section. 

The enolate ions of ketones have become the most widely studied nucleophiles in SrnI reactions [21-23,40,66]. The enolate ions of acyclic and cyclic ketones (from cyclobutanone to cyclooctanone) [21,40] react with aryl and heteroaryl halides to afford the a-arylation products. No... 

Koga and coworkers have investigated the steric effect of the 4-substituent in the deprotonation of cyclic ketones. Small substituents (e.g. R = Me) gave silylenol ether in 46% ee using (R)-25 as chiral base and the ee increased up to 78% with larger aryl substituents (R = Ph, i-Pr, f-Bu)50. 

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