Dialkyl and aryl-alkyl ketones

Reactions of organometallic derivatives with ketones, which are less electrophilic than aldehydes, usually require an equimolar amount of a chiral ligand. The first catalytic enantioselective addition of an organometallic reagent, namely ZnPh2, to dialkyl and aryl alkyl ketones was reported in 1998 by Dosa and Fu (Scheme 110).288 The procedure... 

Seebach and Daum (75) investigated the properties of a chiral acyclic diol, 1,4-bis(dimethylamino)-(2S,35)- and (2K,3/ )-butane-2,3-diol (52) as a chiral auxiliary reagent for complexing with LAH. The diol is readily available from diethyl tartrate by conversion to the dimethylamide and reduction with LAH. The diol 52 could be converted to a 1 1 complex (53) with LAH (eq. [18]), which was used for the reduction of aldehydes and ketones in optical yields up to 75%. Since both enantiomers of 53 are available, dextro- or levorotatory products may be prepared. The chiral diol is readily recoverable without loss of optical activity. The (- )-52-LAH complex reduced dialkyl and aryl alkyl ketones to products enriched in the (S)-carbinol, whereas (+ )-52-LAH gives the opposite result. The highest optical yield of 75% was obtained in the reduction of 2,4,6-... 

Lithium aluminum hydride with either 1,2-0-cyclohexylidene-D-glucofuranose or methyl 4,6-0-benzylidene-a-D-glucopyranoside (0.066 mole and 0.5 mole, respectively, with 0.5 mole LiAlH4) does constitute an asymmetric reduction system (Landor et al., 1964). Unsaturated ketones [e.g., (C.H3)2C=CHCOCH3 and CH3COC= CH] as well as dialkyl and aryl alkyl ketones have been reduced to optically active alcohols. The maximum per cent asymmetric reduction (14%) was observed with acetophenone and 1,2-0-cyclohexylidene-D-glucofuranose. 

A C2-symmetric copper-bound NHC gives excellent ees in fast room-temperature hydrosilylation of dialkyl and aryl alkyl ketones. ... 

Keywords Dialkyl and aryl-alkyl ketones, diethyl/diphenylsilane, CuPhEt (I), KO Bu, THF, room temperature, enantioselective hydroxysilylation... 

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. 

The dimerization of ketones to 1,2-diols can also be accomplished photochemi-cally indeed, this is one of the most common photochemical reactions. The substrate, which is usually a diaryl or aryl alkyl ketone (though a few aromatic aldehydes and dialkyl ketones have been dimerized), is irradiated with UV light in the presence of a hydrogen donor such as isopropyl alcohol, toluene, or an amine. In the case of benzophenone, irradiated in the presence of 2-propanol, the ketone molecule initially undergoes n — k excitation, and the singlet species thus formed crosses to the T, state with a very high efficiency. 

Various aryl-alkyl ketones and dialkyl ketones could be reduced using the Rh(III) - NHC catalyst 55 in high yields (82-96%) and with good to excellent enantioselectivities (67-98% ee) (Scheme 34). 

Another approach in the use of chiral S/P ligands for the hydrosilylation reaction of ketones was proposed more recently by Evans et Thus, in 2003, these workers studied the application of new chiral thioether-phosphinite ligands to enantioselective rhodium-catalysed ketone hydrosilylation processes. For a wide variety of ketones, such as acyclic aryl alkyl and dialkyl ketones as well as cyclic aryl alkyl ketones and also cyclic keto esters, the reaction gave high levels of enantioselectivity of up to 99% ee (Scheme 10.44). 

In summary, a number of effective chiral reducing agents have been developed based on the modification of LAH. Excellent results have been obtained with aryl alkyl ketones and a,p-acetylenic ketones. However, dialkyl ketones are reduced in much lower enantiomeric excess. This clearly indicates that steric effects alone do not control stereoselectivity in these reductions. Systematic studies have been carried out with the objective of designing improved reagents. A better understanding of the mechanisms and knowledge of the active species is required in order to provide more accurate models of the transition states of the key reduction steps. 

Complex 32 has been employed in the asymmetric hydrosilylation of ketones, displaying good activity and excellent enantioselectivities (92% < ee < 98%) for aryl-alkyl ketones, while the selectivity observed in the transformation of the more demanding dialkyl ketones is somewhat lower (67% < ee < 96%). 

Asymmetric reduction of ketones.1 Lithium aluminum hydride, after partial decomposition with 1 equiv. of 1 and an amine additive such as N-benzylmethylamine, can effect asymmetric reduction of prochiral ketones at temperatures of — 20°. The highest selectivity is observed with aryl alkyl ketones (55-87% ee), but dialkyl ketones can be reduced stereoselectively if the two groups are sterically different. Thus cyclohexyl methyl ketone can be reduced with 71% ee. 

Selective reduction of aldehydes. In the absence of radical initiators, tributyltin hydride does not ordinarily reduce carbonyl groups. However, when slurried in cyclohexane with dried silica gel (activated by heating at 220° under reduced pressure), this hydride reduces aldehydes and ketones to alcohols in high yield. The rate of reduction is aldehydes > dialkyl ketones > aryl alkyl ketones > diaryl ketones. Thus it is possible to reduce aldehydes selectively. The function of Si02 apparently is that of a mild acid catalyst. 

Itsuno s amino alcohol (70), prepared from L-valine, is an extremely efficient auxiliary for enantioselective reduction of aryl alkyl ketones using BH3. The corresponding alcohols are obtained in up to 100% ee using BH3 and 0.5 equiv. of (70) in THF at 30 °C. Reduction of dialkyl ketones affords (R)-carbinols in 55-73% ee. Halomethyl t-butyl ketones are also converted to the corresponding (5)-carbinols in high optical purity (Scheme 15). Immobilized amino alcohol (70) permits reduction in a continuous flow system. 1-Phenylpentanol of 90% ee was prepared by this catalytic process in almost 1000% chemical yield based on the quantity of chiral auxiliary used. ... 

Substrates suitable for the Colvin rearrangement have been extended to enolizable aryl alkyl ketones and both aromatic and aliphatic aldehydes using TMSC(Li)N2 (eq 47). These conditions are reported to be superior to those employing dimethyl diazomethylphosphonate (DAMP) with regard to reaction times and range of permissible substrates. However, the reaction is not suitable for dialkyl ketones (see eq 42). ... 

Arylthallium bis(trifluoroacetate)s are converted by successive treatment with KF and BF3 into aryl fluorides.Thallium(iii) nitrate (TTN) readily oxidizes dialkyl sulphides and selenides to the corresponding sulphoxides or selenoxides, and 2-(alkylthio)-l-arylethanones (37) into compounds (38) in methanolic solution.In a modification of the TTN oxidative conversion of aryl alkyl ketones into arylacetic acids, enol ethers derived from the ketones are used instead of the ketones themselves. This reduces the formation of side products. Cyclic aralkyl ketones (39) may be ring-expanded and alkylated to give compounds (40) via treatment of their Wittig-derived alkenes with TTN/ an extrapolation of the basic reaction discovered previously. 

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