Ketones, aryl methyl carbonylation

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)... 

Tetracarbonylcobaltate anion, generated under PTC conditions, catalyzes the reaction of aryl halides with excess methyl iodide under a CO atmosphere [122]. The reaction produces aryl methyl ketones and carboxylic acids as the main products. Stoichiometric or catalytic iron pentacarbonyl can also be used for the carbonylation of organohalides under PTC conditions [123-128]. For example, reactions of alkyl and arylalkyl halides with CO in aqueous-organic systems using catalytic amounts of Fe(CO)5 and a PT agent afford alkyl- and arylacetic acids as the main products [127]. 

Bromination of carbonyl compounds [1. 162, end of first paragraph]. Jemison8 has reported instances in which nuclear bromination of several aryl methyl ketones predominates over side chain bromination. 

Reaction of Ruthenium Carbonyls with Alkyl Radicals Boese and Goldman reported that in the presence of aryl ketones, d8 metal carbonyls such as Ru(CO)3(dmpe) mediate photocatalytic carbonylation of alkanes via a free radical mechanism.161 The activity was proposed to be initiated by the addition of an alkyl radical to the metal carbonyl and the formation of a metal-acyl radical intermediate. The transition states and the products of the reaction between alkyl radicals and ruthenium carbonyls were studied utilizing the B3LYP level of theory.162 The methyl addition to a carbonyl of Ru(CO)5 or Ru(CO)3(dmpe) was computed to be about 6 kcal/mol more exothermic than addition to free CO. 

The IR spectrum of 2-acetyl-3-methylquinoxaline shows carbonyl stretching absorption at 1695 cm in Nujol and therefore in the region to be expected of an aryl methyl ketone. A range of standard derivatives have been prepared from quinoxalinyl ketones (see Table 1) but cycliza-tion occurs on treatment of various 2-benzoylquinoxalines (10) with... 

Conversion of )C=0 into )CC12 is often carried out by means of PC15. Dropping an aliphatic ketone or aldehyde onto a slight excess of finely powdered PC15 at 0° replaces the carbonyl-oxygen atom by 2C1, but loss of HC1 leads to monochloroethylenes as by-products and these become the main products from aryl methyl ketones.1132... 

On the other hand, Trost used zinc in his bimetallic catalyst. One zinc atom is believed to form the metal enolate, whereas the other acts as a Lewis acid for carbonyl activation. Aldol reactions between branched aldehydes and methyl ketones perform in good yields and excellent selectivities (Scheme 2.117). Besides aryl methyl ketones, simple acetone or methyl vinyl ketone could be used as well [28]. These extensions make this protocol a truly universal method for convergent natural product synthesis. 

For reductive cross-coupling between a,P-unsaturated ketones and aldehydes, Kim et al. made use of In-InCl3 in aqueous media to prepare p,y-unsaturated ketones from methyl vinyl ketone and aryl aldehydes [282] (Figure 8.128). A radical mechanism was proposed, with InCb activating the carbonyl group for cyclopropanation and addition. Uemura also studied the same reaction, with InCl3 (10 mol%) as catalyst, Al as reductant, and requiring the presence of TMSCl [283]. 

The usefulness of the Gewald reaction for the synthesis of 2-amino-3-carbonyl-substituted thiophens has been amply demonstrated during the past two years (c/. ref. 6fl). These thiophens are very useful starting materials for complex condensed systems of pharmacological interest. I.r. and n.m.r. studies showed some anomalies which were interpreted in terms of electron delocalization in the enaminocarbonyl structure. From cyanoacetamide, benzylacetone, and sulphur, the thiophen (9) was obtained. 3-Aryl-substituted derivatives such as (10) were obtained from the appropriate aryl methyl ketone, ethyl cyanoacetate, and sulphur. It has been claimed that (11) is obtained from the reaction of acetoacetic acid anilide with malononitrile and sulphur. This hardly seems to be correct, as (12) is the product expected in the Gewald reaction. It was found that 2-amino-3-ethoxycarbonyl-thiophens (13) react with sodium ethoxide in ethanol, pre-... 

Reduction of aryl alkyl ketones with 78 was quantitative and (- )-/V-meth-ylephedrine was recovered with no loss in rotatory power. High optical yields were obtained with linear aliphatic chains in the ketone, but branching a to the carbonyl group lowered the optical yields significantly. Reduction of aliphatic methyl ketones with 78 at 0°C gave (S)-carbinols in low optical yield (14 to 46%). 

The synthesis of radioactive ketones with C in carbonyl was achieved by carbonylative cross-coupling of aryl iodides or triflates with methyl-, phenyl-, or 2-thienylboronic acids under elevated pressure of CO. To ensure fast reaction, harsh conditions were used. Interestingly, under such conditions the addition of a base is not necessary (Equation (18))." ... 

Ketones have an acyl group with another alkyl or aryl group connected to the carbonyl carbon. Many steroid hormones contain ketone functionality, e.g. testosterone and progesterone. The simplest ketone is acetone (CH3COCH3), where the carbonyl carbon is bonded to two methyl groups. 

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