Ketones methoxylation

In a study of stereochemistry, the half ether (5) of an unsymmetrical diol (6) was required. There is little prospect of making (5) from (6) as chemoselectlvity presents a formidable problem. Grignard disconnection from the tertiary alcohol would leave o-methoxyl ketones (7) or (8). 

Using an identical process, the pipecolic acid derivative (112) was converted into a bicyclic amide derivative as shown in Scheme 36. In this case, the methoxylated amide proved to be unstable in the crude electrolysis reaction and was taken directly into the cyclization-ozonolysis sequence. A 74% yield of the bicyclic ketone was obtained over three steps. Compound (114) was converted into A58365B demonstrating that the anodic oxidation reaction allowed for rapid access to both natural products. 

Transformation of amines to aldehydes or ketones can be carried out via the anodic a-methoxylation of the corresponding carbamates, (4), followed by an acid-catalyzed conversion of the a-methoxylated... 

The title compounds, important anti-inflammatory pharmaceuticals, can be synthesized starting from aromatic ketones, as depicted in the accompanying scheme, involving the above-described detellurative methoxylation in the key step. - ... 

Carboxylic acids can be converted to symmetrical ketones by pyrolysis in the presence of thorium oxide. In a mixed reaction, formic acid and another acid heated over thorium oxide give aldehydes. Mixed alkyl aryl ketones have been prepared by heating mixtures of ferrous salts.1717 When the R group is large, the methyl ester rather than the acid can be decarb-methoxylated over thorium oxide to give the symmetrical ketone. 

Enantioselective alkylation of ketones. Chiral imines prepared from cyclic ketones and 1 on metalation and alkylation are converted to chiral 2-alkyleyclo-alkanones in 87-100% enantiomeric purity.1 The high cnantioselectivity is dependent on chelation of the lithium ion in the anion by the methoxyl group, which results in a rigid structure. 

Very little work has been done on selectivity in anodic reactions of pyridines. Selective methoxylation and acetoxylation are known for al-kylbenzenes, but such reactions have not been reported for alkylpyridines. Also, reports on the oxidation of pyridines having aldehyde, ketone, halogen, hydroxyalkyl, or aminoalkyl functionalities are sparse. 

Silyl-l,3-dienes undergo anodic methoxylation in methanol to give 1,4-addition products with an allylsilane structure as intermediates. Therefore, they are further oxidized to give l,l,4-trimethoxy-2-butene derivatives as the final products. The products are easily hydrolyzed to provide the corresponding y-methoxy-a, /t-unsaUirated aldehydes. Since 1-trimethylsilyl-l,3-dienes are readily prepared by the reaction of the anion of l,3-bis(trimethylsilyl)propene with aldehydes or ketones, l,3-bis(trhnethylsilyl)propene offers a, /i-formylvinyl anion equivalent for the reaction with carbonyl compounds (equation 15)16. 

Some deviations from this normal route which involves an oxirane intermediate occurred in sterically hindered ketones. For example, 2,2,6,6-tetramethyl-4-piper-idine underwent a-methoxylation (20%) [19], whereas cholestanone yielded a product of Favorski-type rearrangement [21], In 17-acetylated steroids the reaction with DIB-MeOH-KOH was normal but in 17-hydroxy-17-acetyl-steroids intramolecular cyclization occurred with formation of oxetanones [22] ... 

Methoxyonychine (136) has been found so far only in G. dielsiana (22). Its relationship to onychine was obvious from its spectra, which also allowed the single methoxyl group to be placed para with regard to the ketone function. The formula published initially, however, was based on the l-aza-4-methylfluorenone skeleton (22). The revised structure (136), confirmed by synthesis using an extension of Koyama s preparation of onychine (84), was published subsequently... 

Reductive amination of methyl ketoreserpate was studied in detail. The use of re-propylamine in the presence of a palladium-charcoal catalyst led not only to the expected mixture of a- and /3-amino derivatives (X), but also to a methyl 17-demethoxy-18-deoxy-l 8-re-propyl -aminoreserpate (XII). In the last case, no attempt was made to define the stereochemistry at C-16 and C-18. Similar eliminations of the C-17 methoxyl under basic conditions were also encountered with other ketone derivative. Reductive aminations were also effected with secondary amines. Piperidine yielded as the sole insolable product the... 

The carbon atom, C-3, which in the kopsinine subgroup bears a carbo-methoxyl substituent, has been shown by the mass spectral evidence summarized above not to be in the six-membered ring which contains Nb. That it lies in a strained six-membered ring is indicated by degradation of the carbomethoxyl groups of refractine (CL-A) and aspidofractine (CXLIII-A) to C-3 ketones (CXLIX-P and CXLII-P), whose IR-absorption occurs at unusually low wavelengths (5.76-5.78 p) (Section III, G). 

Of some interest is the ease of hydrolysis of the aliphatic methoxyl groups of these alkaloids which, in common with the sharp drop in pK a (33% dimethylformamide) which is observed on passing from the alcohol, CXXV (7.25), to the ketone, CXXXIII (5.90), would seem to point to an interaction with Nb. Examination of models does not show proximity between these two positions, however. A similar change in basicity is seen in the pairs, ajmalidine (ketone, pK a 6.3) and sandwicine (alcohol, pK a 8.5) (98, 99), and kopsine (ketone, pK a 4.28) and dihydro-kopsine A (alcohol, pK a 6.1) (109, 100). The two ketones, like CXXXIII,... 

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