Asymmetric aryl ketones

In another context, chiral thioimidazolidine ligands have been successfully applied to the ruthenium-catalysed asymmetric hydrogen transfer of several aryl ketones by Kim et al., furnishing the corresponding chiral alcohols with high yields and enantioselectivities of up to 77% ee (Scheme 9.12). ... 

Chan has discovered a completely atropdiasteroselective synthesis of a biaryl diphosphine by asymmetric intramolecular Ullmann coupling or Fe(m)-promoted oxidative coupling. A chiral atropisomeric biaryl bisphosphine ligand 2 was synthesized through this central-to-axial chirality transfer.38 Recently, a xylyl-biaryl bisphosphine ligand, Xyl-TetraPHEMP, was introduced by Moran, and is found to be effective for the Ru-catalyzed hydrogenation of aryl ketone.39... 

The asymmetric arylation of ketone enolates represents an attractive method for the preparation of optically active carbonyl compounds with a stereogenic quaternary center at the a-position to the carbonyl group. Such types of compounds are important intermediates for natural product synthesis. Replacement of BINAP by 109 provides... 

It is well accepted that the asymmetric reduction of simple dialkyl ketones generally proceeds with low enantioselectivity.68 Ohkuma et al.69 reported that hydrogenation of simple ketones can be achieved using Ru(II) catalysts in the presence of diamine and alcoholic KOH in 2-propanol. Promising results have been achieved in the asymmetric hydrogenation of alkyl aryl ketones with a mixture of an Ru-BINAP complex, chiral diamine, and KOH (Scheme 6-33). 

The quininium and quinidinium fluoride catalysts, 10 (R=H etc., X=F) and 8 (R=H, X=F), were used for the asymmetric reduction of alkyl aryl ketones in conjunction with silanes.1751 One of the most efficient silanes proved to be tris(trimethylsiloxy)silane, which together with 8 (R=H, X=F) reduced acetophenone to give the alcohol 102 in almost quantitative yield with 78 % ee, as shown in Scheme 31. The... 

Scheme 31. Asymmetric reduction of alkyl aryl ketones.

Asymmetric reductions. The reagent can effect asymmetric reduction of alkyl aryl ketones and unhindered dialkyl ketones in high optical yield.1 It is the most useful reagent known to date for asymmetric reduction of even hindered a-keto esters to (S)-a-hydroxy esters in >90% ee.2 It is also effective for asymmetric reduction of phosphinyl imines of dialkyl ketones, RlR2C=NP(0)(C6H5)2 (50-84% ee).3... 

A further example of the use of a chiral anion in conjunction with a chiral amine was recently reported by Melchiorre and co-workers who described the asymmetric alkylation of indoles with a,P-unsaturated ketones (Scheme 65) [212]. The quinine derived amine salt of phenyl glycine (159) (10-20 mol%) provided the best platform with which to perform these reactions. Addition of a series of indole derivatives to a range of a,P-unsaturated ketones provided access to the adducts with excellent efficiency (56-99% yield 70-96% ee). The substrates adopted within these reactions is particularly noteworthy. For example, use of aryl ketones (R = Ph), significantly widens the scope of substrates accessible to iminium ion activation. Expansion of the scope of nucleophiles to thiols [213] and oximes [214] with similar high levels of selectivity suggests further discoveries will be made. 

Fluorination of sulfonamides 147 and 148 takes place upon deprotonation with NaH and reaction with perchloryl fluoride, FCIO3, to give products 149 and 150 (Scheme 19) <2000JOC7583, 2000CPB1954>. The resulting A-fluorosultams 149 and 150 have been used for the asymmetric fluorination of aryl ketone enolates (vide infra). 

A-Boc-leucinal may react with allyl- and alkenyhnagnesium hahdes giving syn- and awf/-products in ca 9 1 ratio. This method was used for the asymmetric synthesis of important amino acids like statine and norstatine. An enantioselective desymmetrization of anhydrides was reported. Arylmagnesium chlorides react in toluene in the presence of (—)-sparteine (1 equiv.) with 3-substituted glutaric anhydrides 215, giving aryl ketones with 87-92% ee (equation 145). ... 

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... 

Asymmetric reduction of ketonesLithium aluminium hydride in conjunction with this chiral ligand reduces prochiral aromatic ketones to (S)-secondary alcohols in 90-95% optical yields. Optical yields are lower (10-40% ee) in the case of alkyl aryl ketones. It is superior to (S)-2-(anilinomethyl)pyrrolidine for this reduction. Evidently the two methyl groups enhance the enantioselectivity. 

Asymmetric reduction of ketones. Ipc BCl is somewhat superior to B-3-pin-anyl-9-borabicyclo[3.3.1]nonane (12, 397) for enantioselective reduction of alkyl aryl ketones at normal pressures to (S)-alcohols. In general, optical yields are 78-98%. It is also useful for asymmetric reduction of ketones in which one alkyl group is tertiary. Thus 3,3-dimethyl-2-butanone is reduced in 95% ee at 25°.1... 

Asymmetric hromination of ketals of alkyl aryl ketones,l a-Bromination of the ketals of alkyl aryl ketones obtained with the dimethyl esters of (2R,3R)- or (2S,3S)-tartaric acid is highly diastereoselective. Hydrolysis of the products provides optically active 2-bromo ketones. 

Asymmetric reduction of alkyl aryl ketones with trialkoxysilanes is promoted by a catalytic amount of chiral nucleophiles [39]. The reactive species is a transiently prepared hypervalent silicon hydride. 2, 4, 6 -Trimethylacetophenone was reduced with equimolecular amounts of trimethoxysilane in the presence of the monolithio salt of (R)-BINAPHTHOL (substrate Li=20 l) in a 30 1 ether-TMEDA mixed solvent at 0 °C to afford the R product in 90% ee (Scheme 21) [40]. The presence of TMEDA was crucial to achieve high yield and enantiose-lectivity. Reduction of less hindered ketonic substrates preferentially gave the... 

Buchwald has designed a hindered dialkylphosphino-binaphthyl ligand (3) that is much more active than the original ligand for asymmetric arylation of ketone enolates. Reactions occur at room temperature using only 2 mol % catalyst with enantioselectivities up to 94% [41]. Additionally, the Buchwald group has developed an electron-rich monodentate ligand (4) capable of vinylation of ketone enolates with up to 92% ee [42]. 

The majority of recent publications still deal with the chiral hydrogenation of ketones containing other functional groups as well. The general characteristics of these reactions are illustrated by the asymmetric hydrogenation of a./f-unsaturated ketones. In addition, the purpose of the present review is to summarize the latest results of the chiral hydrogenation of ketones which do not contain other functional groups (dialkyl ketones and alkyl aryl ketones). 

Asymmetric reduction of alkyl aryl ketones. The complex (2) derived from lithium aluminum hydride and this diamino alcohol (1), prepared from (S)-( — )-... 

E. Katayama, T. Yokozawa, T. Ikaeiya, and R. Noyori, Asymmetric hydrogenation of alkenyl, cyclopropyl, and aryl ketones. RuCl2(xylbinap)(l,2-diamine) as a precatalyst exhibiting a wide scope, J. Am. Chem. Soc. 1998, 120, 13529-13530. 

Intermolecular a-arylation of the ketone 399 with o-tolyl bromide (398) gives 400 under selected conditions using f-BuONa or KN(SiMe2)2 as suitable bases, and BINAP or DPPF (XLIX) as a bulky ligand [194], Furthermore, asymmetric arylation of the ketone 402 with the bromide 401 gave 403 with 98% ee efficiently by using chiral BINAP [195]. 

The asymmetric hydrogenation of aryl ketones is an important step in the synthesis of many pharmaceutical intermediates. Blaser and co-workers showed that Ru complexes with Fe-cyclopentadienyl sandwich complexes are good catalysts for this reaction [63]. Figure 1.26 shows the different substrates tested, along with the time, conversion, and substrate/catalyst ratio. Using these data, calculate the catalyst TON and TOF in each case. 

---