Methyl aryl ketone

The Willgerodt reaction starts with the formation of an enamine 4 from the ketone, e.g. from acetophenone 3. The further course of the reaction cannot be described by a single mechanism that would apply to all examples known. For aryl methyl ketones 3 the mechanism for the Kindler variant is formulated as follows ... 

Ketones used in this report are reduced by the cyanobacterium with excellent enan-tioselectivities (> 96% ee). An enzyme exhibiting high enantioselectivity usually shows a relatively strict substrate specificity hence, there scarcely is a catalyst that reacts with many kinds of substrates and also shows high select vities. This alga can reduce a wide variety of aryl methyl ketones and afford the corresponding alcohols with high enantioselectivities. 

Several other ehiral S/O ligands have been involved by Yang and Lee in this type of reaetions, sueh as [(lf ,25 ,3f )-3-mercaptocamphan-2-ol)], MerCO, whieh produeed, when applied to aryl methyl ketones, the corresponding 1-aryl ethyl alcohols in enantioselectivities of up to 92% ee (Scheme 10.63)." ... 

Scheme 10.63 Borane reductions of aryl methyl ketones with MerCO ligand.

Scheme 34 Cu-catalyzed asymmetric reaction of aryl methyl ketones and methyl acrylate...

Scheme 28.18 Enantioselective hydrogenation of aryl-methyl ketones.

Recently, the first report was made on the ruthenium-catalyzed enantioselective hydrogenation of aryl-methyl ketones using monodentate phosphonites (Scheme 28.18). In particular, ligand 15f induced excellent ee-values. One very early report on rhodium-catalyzed hydrogenation of ketones using the monophosphine bmpp 1 f met with a low e.e. [95]. 

Aryl methyl ketones have been obtained [4, 5] by a modification of the cobalt-catalysed procedure for the synthesis of aryl carboxylic acids (8.3.1). The cobalt tetracarbonyl anion is converted initially by iodomethane into the methyltetra-carbonyl cobalt complex, which reacts with the haloarene (Scheme 8.13). Carboxylic acids are generally obtained as by-products of the reaction and, in several cases, it is the carboxylic acid which predominates. Unlike the carbonylation of haloarenes to produce exclusively the carboxylic acids [6, 7], the reaction does not need photoinitiation. Replacement of the iodomethane with benzyl bromide leads to aryl benzyl ketones in low yield, e.g. 1-bromonaphthalene produces the benzyl ketone (15%), together with the 1-naphthoic acid (5%), phenylacetic acid (15%), 1,2-diphenylethane (15%), dibenzyl ketone (1%), and 56% unchanged starting material [4,5]. a-Bromomethyl ketones dimerize in the presence of cobalt octacarbonyl and... 

Aryl methyl ketones via the cobalt-catalysed carbonylation of aryl halides (Table 8.16)... 

Furthermore, Rueping and coworkers applied their reaction conditions to the cyanation of ketimines [54]. The use of A-benzylated imines derived from aryl-methyl ketones generally gave comparable yields, but lower enantioselectivities. However, this method furnished Strecker products bearing a quaternary stereogenic center, which are valuable intermediates for the preparation of optically active a,a-disubstituted a-amino acids. 

BINOL phosphate (5)-3o (10 mol%, R = 2,4,6- PTj-C Hj) turned out to be the catalyst of choice and gave iV-acetylated 3-indolyl amines 128 bearing a qnatemary stere-ogenic center in excellent yields (94-99%) with high enantioselectivities (73-97% ee). Enamides derived from aryl-methyl ketones as well as indoles with varions substitnents conld be employed. 

Scheme 6.94 Typical products obtained from the 86-catalyzed Michael addition of aryl methyl-ketone-derived morpholine enamines to various aromatic nitroalkenes and subsequent acidic hydrolysis.

In a related three-component reaction procedure, aryl methyl ketones 724 have been combined with aryl aldehydes 725 and urea 726 at room temperature, using trimethylsilyl iodide as catalyst, to give 4,6-diaryl-3,4-dihydro-2(177)-pyrimidinones 727 <2005HCA2996>. A procedure using zinc iodide and microwave irradiation gave similar products <2007T1981>. 

The aromatic ketones that occur or are used as fragrance and flavor materials are predominantly aryl methyl ketones, which include acetophenones and /3-naphthyl methyl ketone. Several acetylpolymethylindanes and -tetralins are commercially important as musk fragrances. 

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. 

Methyl arylacetates.2 Aryl methyl ketones are converted into methyl arylacetates by reaction with BF3 etherate and lead tetraacetate in benzene at room temperature (equation I). Thallium(lll) nitrate (4, 496) has also been used for this modified Willgerodt-Kindler reaction. 

Mechanistically, the reaction proceeds through Michael addition of the aryl methyl ketone to the enone. Hydride abstraction and cyclization then yield the pyrylium salt. The route is capable of considerable diversification and therefore has much potential. The detailed method for the synthesis of 2,4,6-triphenylpyrylium perchlorate is worthy of mention... 

Nitrones of several aryl methyl ketones were hydrogenated by a catalyst prepared in situ from [IrCl(COD)]2, (S)-BINAP, and (n-C4H9)4NBH4 in THF under 80 atm of H2 and at 0 °C to give the corresponding Af-hydroxylamines in up to 86% ee (Scheme 6) [14]. Substitution of halides at the 3 or 4 position of the ar-... 

As shown in Scheme 1.95, the chiral titanocene catalyst 34 (see Scheme 1.10) prepared from 33, n-C4HgLi, andC6H5SiH3 shows a moderate-to-good enantioselectivity in the hydrogenation of /V-benzyl i mines of aryl methyl ketones, whereas the catalytic activity is rather low even at 137 atm [346]. The ketimine with R1 = 4-CH3OC6H4 is hydrogenated with (/ )-34 to give the R amine with 86% ee. The E Z of the imine substrate affects the enantioselection. The optical... 

Shibasaki has examined catalysis of a complex, prepared in situ from PdCl2, AgOTf, (R)-or (S)-BINAP, 4 A molecular sieves, and H20, in the aldol addition reaction of enolsilanes by (Eq. 8B2.5) [13]. Under these conditions, aryl methyl ketone-derived trimethylsilyl enolates add to benzaldehyde and hydrocinnamaldehyde, affording adducts with up to 73% ee. 

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