Hydroxy aromatic ketones

Finally, the asymmetric hydrogenation of a series of a-hydroxy aromatic ketones in methanol catalyzed by Cp lr(OTf)(MsDPEN) (42, MsDPEN = N-(methanesul-... 

Crafts process is to generate carbonium ions from the alkyl or acyl halides. It would be expected, then, that a number of other combinations of starting materials and reagents which lead to carbonium ions should be capable of effecting acylation or alkylation. Indeed we find that olefins (p. 35), alcohols (p. 36), ethers (p. 36), and esters (p. 37) can be used as starting materials for aromatic alkylation reactions in the presence of such catalysts as boron trifluoride, sulfuric acid, or anhydrous hydrogen fluoride.69 Acylations can be carried out with acids (p. 37),64 acid halides (p. 230), and acid anhydrides (p. 37). The Fries reaction65 (in which phenolic esters are converted to hydroxy aromatic ketones by means of aluminum chloride) appears to be an example of a typical acylation reaction in which the ester itself acts as the source of an acyl carbonium ion ... 

A computational study of the reaction of benzene and other arenes with bromine indicates the inherent competition between substitution and addition processes, and shows that both, 2-cis and 1,4-syn additions may compete with the classical substitution pathway involving Wheland intermediates. The bromination of the dipyrromethene dye (3) has been found to occur in a stepwise manner in the order 2,6- followed by 3,5- and Anally 1,7-positions. There have been kinetic and mechanistic studies of the bromination of sulfanilic acid using A-bromosuccinimide and of salicyclic acid with bromine. The kinetics of the iodination of substituted hydroxy aromatic ketones using iodine and iodic acid have also been reported. " ... 

The product is a P-hydroxy aldehyde (called an aldol) or ketone, which in some cases is dehydrated during the course of the reaction. Even if the dehydration is not spontaneous, it can usually be done easily, since the new double bond is in conjugation with the C=0 bond so that this is a method of preparing a,P-unsaturated aldehydes and ketones as well as P-hydroxy aldehydes and ketones. The entire reaction is an equilibrium (including the dehydration step), and a,P-unsaturated and P-hydroxy aldehydes and ketones can be cleaved by treatment with OH (the retrograde aldol reaction). There is evidence that an SET mechanism can intervene when the substrate is an aromatic ketone. ... 

No stereoselectivity was observed in the formation of a 1 1 diastereomeric mixture of 2-hydroxy-2-phenylethyl p-tolyl sulfoxide 145 from treatment of (R)-methyl p-tolyl sulfoxide 144 with lithium diethylamide . However, a considerable stereoselectivity was observed in the reaction of this carbanion with unsymmetrical, especially aromatic, ketones The carbanion derived from (R)-144 was found to add to N-benzylideneaniline stereoselectivity, affording only one diastereomer, i.e. (Rs,SJ-( + )-iV-phenyl-2-amino-2-phenyl p-tolyl sulfoxide, which upon treatment with Raney Ni afforded the corresponding optically pure amine . The reaction of the lithio-derivative of (-t-)-(S)-p-tolyl p-tolylthiomethyl sulfoxide 146 with benzaldehyde gave a mixture of 3 out of 4 possible isomers, i.e. (IS, 2S, 3R)-, (IS, 2R, 3R)- and (IS, 2S, 3S)-147 in a ratio of 55 30 15. Methylation of the diastereomeric mixture, reduction of the sulfinyl group and further hydrolysis gave (—)-(R)-2-methoxy-2-phenylacetaldehyde 148 in 70% e.e. This addition is considered to proceed through a six-membered cyclic transition state, formed by chelation with lithium, as shown below . ... 

In the presence of strong alkali, the rhodium analog of 62, or RhCl(C8H,2)PPh3, hydrogenates aliphatic ketones at 1 atm and 20°C, and after treatment with borohydride the systems similarly reduce aromatic ketones to the alcohols (526). Deuterium exchange data for acetone reduction were interpreted in terms of hydrogen transfer within a mononuclear hydroxy complex containing substrate bound in the enol form (63). 

The photocycloaddition of aliphatic and aromatic aldehydes with 2,4,5-trimethyloxazole (131) gave bicyclic oxetanes 132 in almost quantitative yields hydrolitic cleavage led selectively to erytro a-amino-P-hydroxy methyl ketones 133 <00CC589>. The oxazolium salt 134 was converted to the azomethine ylide 136 via electrocyclic ring opening of the oxazoline 135. Intramolecular cycloaddition afforded 137 in 66% overall yield which was transformed into the aziridinomitosene derivative 138 . 

An operationally simple procedure involving a variation of this reaction and relying on the use of a polymer-supported [hydroxy(sulfonyloxy)iodo]benzene with aromatic ketones or alcohols has also been published <2004S2673>. 

The synthesis and characterization of V02+ complexes of hydrazones (94) and (95) derived from benzoylhydrazine and o-hydroxy aromatic aldehydes and ketones were also reported772 and molecular weight determinations, IR, electronic spectra and magnetic properties were explained assuming a dimeric structure (96) with each unit having a five-coordinate square pyramidal geometry. 

Benzofurans from o-Hydroxy-lated Aromatic Ketones... 

Aliphatic aldehydes and ketones and also aliphatic-aromatic ketones can be converted into the corresponding hydrocarbons alkyl-phenols can be obtained from phenolic-aldehydes and -ketones p-hydroxy-benzophenone yields p-benzylphenol benzoin and benzil yield dibenzyl anthraquinone yields anthracene dihydride. 

Other aromatic ketones undergo photocyclization to form oxygen heterocycles. Methyl o-benzyloxyphenylglyoxylate (400) is converted in high yield into a mixture of the isomers (401 and 402).415 The stereochemistry of the cyclization is both solvent- and temperature-dependent, the former isomer (401) being formed almost exclusively in nonpolar solvents such as heptane or benzene, and in each case an excited triplet appears to be involved. The related aldehyde, O-benzylsalicylaldehyde (403), is similarly converted into cis-2-phenyl-3-hydroxy-2,3-dihydrobenzofuran (404), but in much lower yield a second product may possibly be the tram isomer.410... 

The ADH from Lactobacillus brevis (Riebel, 1997) has a broad substrate specificity and converts even bulky aromatic ketones with high activity (Hummel, 1999 Wolberg, 2001). In addition, the enzyme is the best characterized completely (R)-specific ADH. The enzyme belongs to the class of short-chain dehydrogenases and its 3D structure has recently been solved (Niefind, 2003). The recombinant form of L. brevis ADH in E. coli accepts a variety of /j.d-dikelo esters as was determined in the synthesis of potential building blocks for HMG CoA reductase inhibitors (see also Chapter 13, Section 13.3.2) (Wolberg, 2001). tert-Butyl 3,5-dioxohexanoate and tert-butyl 3,5-dioxoheptanoate were reduced on a preparative scale to afford the corresponding (R)-<5-hydroxy-/3-keto esters with 99.4% e.e. and 98.1% e.e., respectively. 

Regio- and stereoselective aldol condensations. The cnol boronates of ketones, obtained by reaction with 1 and diisopropylcthyluminc (1 equiv.), react with both aliphatic and aromatic ketones at —78° to — 15° to form (i-hydroxy ketones with high, yvn-dia-stereoselectivity, ... 

Although beryllium metal is rather sluggishly reactive toward most organic halides, it reacts surprisingly easily with acyl halides in ethyl acetate to form acylberyUium halides. These react normally with ketones by addition, prodncing hydroxy ketones. With aromatic ketones, electron transfer appears to dominate, as the principal prodnct from the ketone is the pinacol. 

RuCl2 P(C6H5)3 3 is used as a precursor in combination with a pyridine-containing derivative of 2-amino-2 -hydroxy-l,T-binaphthyl [272], and an amino bisoxazo-line ligand, AMBOX (16) [273], effecting the enantioselective reduction of several aromatic ketones with up to 98% e.e. The enantioselectivity is decreased by increasing the bulldness of alkyl groups. 

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