Cyclic aryl ketones yields

Good yields of cyclic aryl ketones are achieved with arenes, provided they are not very electron deficient. For example, the cycloacylation of arylpropanoic acids can be performed in the presence of scandium triflate as Lewis acid to give indanones in good yields with electron-rich aromatic substrates, whereas lower yields are obtained with very electron-deficient ones. The reaction can also be performed in the presence of protic acid thus, 3-(3,5-dibromophenyl)propanoic acid is directly converted into... 

The synthetic application to different arylalkanoic acids is reported in Table 2.4, showing that cyclic aryl ketones can be produced in high yields under very mild conditions. 

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... 

However, intramolecular O-alkylation can be performed under particular conditions leading to of annelation of a seven-membered heterocycle. Japanese researchers (170) prepared the corresponding seven-membered cyclic nitronates (50a-c) in good yields by the reaction of triethylamine with brominated aryl ketones (49a-c) containing the nitromethyl group in the ortho position. 

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]. 

Asymmetric reduction of a,fi-enon s. This combination of reagents (1 1) in conjunction with N-cthylaniline (2 equivalents) reduces alkyl aryl ketones to alcohols with high stereoselectivity.1 Under these conditions 2,/1-unsaturated ketones arc reduced to optically active (S)-allylic alcohols. Optical yields of 80 98% have been reported for open-chain enones. Reduction of cyclic enones is somewhat less efficient. The method was used to reduce 1 to 2, which has been used as an intermediate in an anthracyclinone synthesis.2... 

Enol Amination. The Cu[(S,5)-t-Bu-box] (OTf)2 complex was found to be optimal for promoting the enantioselective conjugated addition of enolsilanes to azodicarboxylate derivatives (eq 13). This methodology provides an enantioselective catalytic route to differentially protected ot-hydrazino carbonyl compounds. Isomerically pure enolsilanes of aryl ketones, acylpyrroles, and thioesters add to the azo-imide in greater than 95% ee. The use of an alcohol additive was critical to achieve catalyst turnover. Amination of cyclic enolsilanes was also possible. For example, the enolsilane of 2-methylindanone provides the adduct containing a tetrasubstituted stereogenic center in 96% ee and high yield. Acyclic (Z)-enolsilanes react in the presence of a protic additive with enantioselection up to 99%. ... 

The outlined Nugent reductive amination protocol with (R) or (S) PEA and prochiral alkyl alkyl and aryl alkyl ketones (acydic or cyclic) allows higher yields and shorter reaction times than the previously practiced two step strategy via isolated (R) or (S) PEA, see Moss, N., Gauthier, J., and Ferland, J. M., (1995) Synlett, 142 144 ... 

The first example of the use of aryl benzenesulfonates as arylating species in a-arylation reactions of acyclic and cyclic ketones was reported by Buchwald and coworkers [49] in 2003. A catalytic system composed of a mixture of Pd(OAc)2 and 2-dicyclohexylphosphino-2, 4, 6 -triisopropylbiphenyl (XPhos), allowed the synthesis of the required a-arylated ketones in very good yields (Scheme 8.21) [49]. 

Aryl ketones can be aminated also using as catalyst the amine 27 derived from cinchona alkaloids (20 mol%) [35]. For this reaction, the addition ofp-toluenesulfonic acid (40 mol%), and 4 A molecular sieves was compulsory in order to achieve good enantioselectivities. Under similar conditions, aryl ketones, such as propiophe-nones, butyrophenones, heteroaryl ketones or even cyclic 1-tetralone, and diethyl azodicarboxylate (18a) in isopropanol as solvent, yielded at 40°C the aminated product in good results (39-77%, 88-97% ee). 

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. 

---