A-Aryl methyl ketones

Protonation of nitroalkenes. This strong acid diprotonates nitroalkenes, even nitroethylene, to give N,N-dihydroxyiminium carbenium ions, which react with arenes to give arylated oximes. This overall process provides a route to a-aryl methyl ketones from 2-nitropropene.1... 

The selective Pd-catalysed mono-a-arylation of acetone with aryl chlorides, bromides, iodides, and tosylates has been reported. The reaction makes direct use of a simple and abundant three-carbon feedstock without the requirement of stoichiometric additives or preformed enolates to generate a -aryl methyl ketones. In view of the excellent selectivity and functional group tolerance, and the relative mildness of the reaction conditions, this protocol appears to be widely adopted in synthetic chemistry. 

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. 

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... 

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. 

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>. 

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. 

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. 

A mixture of aryl methyl ketone 1 (1 mmol) and [hydroxy(tosyloxy)iodo]ben-zene (1.2 mmol) taken in a glass tube, was placed in an alumina bath inside the MW oven and irradiated for 30 s at 50% power level. After completion of the reaction, as determined by TLC examination, the crude product was washed with hexane to afford pure tosyloxymetliyl aryl ketone 2. 

Olah and Ip999 showed that Nafion-H catalyzes condensation of acetone to give mesitylene999 [Eq. (5.361)]. In contrast to phosphoric acid and sulfuric acid, the reaction carried out in a flow system gives the product with high selectivity. Likewise, substituted aryl methyl ketones can be transformed to 1,3,5-triarylbenzenes1000 [Eq. (5.361)]. orf/zo-Substituted acetophenones, however, do not react. 

The oxidation of an aryl methyl ketone, with selenium dioxide [Method (a)] in a suitable solvent, to an aryl 1,2-ketoaldehyde is illustrated by the preparation... 

Aryl methyl ketones can only give a single enol (or enolate ion) and subsequent reactions are therefore entirely regioselective. These include halogenation (cf. Section 5.11.1, p. 667), and the Mannich reaction (cf. Section 5.18.2, p. 801). 

Asinger s studies demonstrated that product formation is sensitive to the ratio of sulfur to ketone (1), the structure of the ketone, the replacement of ammonia by amines, the temperature and the medium. Room temperature (20-25 °C) reactions in which the ratio of sulfur to ketones is 0.5 favors the formation of 3-thiazoline, 2, as shown in Figure 1. The formation of 5-alkylidene-3-thiazolines, 3, sometimes competes with the formation of 3-thiazolines such is the case when aryl ketones such as l-phenylpropan-2-one and l-phenylbutan-2-one are employed (4). Also the additional presence of hydrogen sulfide promotes the generation of 1,2,4-trithiolanes and 1,2,4,5-tetrathiolanes from ketones ana aldehydes at the expense of 3-thiazoline formation (11-12). Increasing the S/ketone ratio to 8 favors the formation of the 3-imidazoline-5-thione (5), a product which has a greater tendency to result from aryl methyl ketones (3). 

The reaction of 2//-pyran-2-ones 24 with aryl methyl ketones in the presence of KOH provides a mixture of 1,3-teraryls 25 and alkylidenc-2//-pyrans 26 (Equation 13) <1998S167>. Likewise, 6-(4-fluorophenyl)-3-cyano-4-(methylthio)-27/-pyran-2-one 27 reacts to afford the corresponding alkylidene 2//-pyran as the sole product (Equation 14) <2001J(P1)1953>. 

Preparation of the JST class (see Section 12.3.4) of the ruthenium-diphosphine-diamine complex, [(PhanePhos)Ru(diamine)Cl2], produced highly active and enantioselective catalysts in the reduction of aryl methyl ketones (128, R = Me), as well as a,P-unsaturated ketones.162-163 Higher... 

A new type of lanthanoid complex, prepared from BINOL and SmCl3, served as an asymmetric catalyst for MPV reduction of aryl methyl ketones in the presence of molecular sieves. Moderate enantioselectivity was obtained.101... 

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