Monocyclic ketones derivatives

Monocyclic tetrahydrophosphorin derivatives can be prepared, for example by dehydration of tertiary alcohols which are available by the action of lithium alkyls on 4-oxophos-phorinane derivatives (equation (16)). P- Oxidation and dehydrogenation of the ketone with Se02 is also possible (equation (17)) (66AG(E)588). Electrophilic substitution in position 2 (6) of phosphorinane 1-oxides and 1-sulfides can be achieved by a Wittig-Horner a-deprotonation, e.g. equation (18) (72BSF(2)402l, 79CJC723). 

Many rotatory dispersion curves have been obtained for optically active ketones derived from steroids and triterpenes, which are monocyclic, bicyclic, and open-chain compounds. Enough data have been accumulated so that the various shapes and magnitudes of the curves are recognized as characteristic of particular structural features. A good illustration is provided by the rotatory... 

The most widely used method for the introduction of angular subsituents is the direct alkylation of cyclic ketones with keto groups at C5 (Scheme 74), Ci7 (Scheme 27), and (Schemes 85, 97-99, and 102), The features of these reactions are conveniently discussed in the case of a bicyclic model compound, 1-decalone (51), which represents the CD moiety of the steroid molecule. While in the alkylation of monocyclic ketones the attack of the alkylating group takes place mainly at a tertiary carbon atom, in the case of decalone (51), instead of the expected angularly-alkylated 9-methyl derivative (50) the 2-methyl derivative (52) is formed as the product of attack on a secondary carbon atom [38, 39], This makes it necessary to protect position 2 and thereby to direct the attack of the alkylating agent to position 9. 

A relevant biogenetic-type rearrangement is observed in the acid-catalyzed cyclization of the terminal epoxide (386) of 7-farnesyloxy-coumarin (umbelliprenin) 480). The friedelin-like, monocyclic ketone (388), obtained in 4% yield along with several other products, presumably arises from the monocyclic carbon ion intermediate (389) through a sequence of 1,2-shifts. Sesquiterpene derivatives of this type e.g., asco-chlorin, 390) are, in fact, mold metabolites 481). The pattern of in-... 

Acyl substituents at the 3- and/or 4-positions result in decreased hydrolytic stability compared with the alkyl and aryl derivatives described above. Despite this constraint most of the usual reactions of the carbonyl group are possible. Aldehydes <9ILA1211> and ketones are oxidized to the carboxylic acid, borohydride reduction affords the expected alcohols, and epoxides are formed on reaction with diazomethane. Oximes and arylhydrazones are formed with hydroxylamine and arylhydrazines, and the products may subsequently undergo monocyclic rearrangement involving the oxadiazole to give the corresponding isomeric furazans and 1,2,3-triazoles (Section 4.05.5.1.4). 

Reactions of this type provide major routes to both the monocyclic system and to 1,5-benzothiazepines. In some cases the reactions are single-stage processes but in many cases the intermediate produced by the primary formation of the S—C bond can be isolated. Thus 2-aminoethanethiol reacts with a,/3-unsaturated or j3-halogeno ketones to give (408). Similarly reaction with a,/3-unsaturated acids, esters or acid chlorides and with 3-halogenopropionyl halides gives the 5-oxo derivative (409). 2-Aminoethanethiol also reacts with activated 2-chlorobenzophenones to give 1,4-benzothiazepines. 

Monocyclic phenols and their methyl ethers react with benzene in HF—SbF5 medium to provide 4,4-disubstituted cyclohexenones 237 [Eq. (5.308)].3O1para-Methylanisole gives three products two cyclohexenone derivatives [see Eq. (5.112)] and an interesting tricyclic ketone 238. 

For monocyclic and many fused bicyclic ketones the general order of reactivity of3>4>6>7 5 has been observed in the reaction with diazomethane and derivatives. Cyclopropanones react smoothly with diazomethane and diazoethane in the absence of catalysts to form cyclobutanones (equations 1 and 2). ... 

Monocyclic pyrones are derived by formylation of various simple ketones. Thus, dibenzyl ketone yields 3,5-diphenyl-4-pyrone,79 while benzoylacetone gives 3-benzoyl-4-pyrone (Scheme 30).44... 

The reaction of monooxo C-H acids such as acetone/ ethyl methyl ketone,or cyclo-pentanone with monocyclic A, 0-acetals or bicyclic A, 0-acetals or aminals gave the expected substitution products 1. Aqueous buffer solutions of pH 5.5 were reported to be sufficient for activation of bicyclic aminal precursors. Monocyclic aminal or hemiaminal starting materials were less reactive. Remarkably, methyl cyanoacetate could not be aminocyclopropylated. The sterical course of the reaction of bicyclic derivatives was not determined. 

Oxidation of tetraterpenes yields many compounds, and the cyclic compounds with a trimethylcyclohexane ring are easily associated with degradation of monocyclic and bicyclic carotenes, but allylic compounds are now as conspicuous in their biogenetlc origin. Many such compounds are derived from lycopene, phytoene and phyto-fluene, three very common acyclic carotenes. These allylic compounds are often identified only as terpene aldehydes and ketones and not as carotene degradation products (10). 

Doering et al." extended this application to the synthesis of tricyclic ketones from monocyclic diazoketones, using as catalyst copper powder, cupric sulfate, or cuprous iodide with apparently equal success. A sketchy advance report,12 claims the synthesis of 8,9-dehydroadamantane-2-one (5, m.p. 206.5-207.5°) via the acid chlorides (3) and (4) and the derived diazoketones. 

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