3-methyl-4-keto derivatives

Polymer-supported quaternary ammonium hydroxides have been used to catalyse Michael reactions between various alkyl methacrylates, acrylonitrile, and methyl vinyl ketone as acceptors and nitro or keto derivatives as donors.[116,117]... 

Hydroxymethyl-4-methyl steroid derivatives (177) have been prepared from 4-en-3-ones (173) by reductive methoxycarbonylation (Li-NH3, C02, then methylation with CH2N2), followed by methylation of the /3-keto-esters (175) and finally reduction with LiAlH4 to give separable isomeric diols (177).165... 

The tetrahydrodiazepine (112) was found107 to be a highly unstable substance. On the other hand, the 4-keto derivative (110, R = H) was quite stable, although refluxing a dilute aqueous hydrochloric acid solution led to the formation of what was believed to be an oxindole polymer. This ready acid hydrolysis was attributed to the essentially acetal-like character of the grouping N—CH2—N. The low basicity of 110 (R = H) (pK < 2) is of interest since A-methyl-o-toluidine has a pK of 4.87. The inductive effect plus the mesomeric influence of the amide carbonyl and internal strain effects resulting in a certain amount of bond opposition appear to explain this basicity.107... 

Although a 14-OH group did not enhance the activity of 6-azido-4,5-epoxymorphinans, the presence of a 14/3-methyl group (188) afforded an RTF sc activity of 5000 x morphine. The corresponding 14/3-ethyl 6-keto derivative (189) was 104 as potent as morphine ... 

The a-methyl derivative is produced from the acetate of o-allylphenol, HOC4H6CHjCH= CHj, by the addition of hydrogen bromide in the absence of peroxides followed by dehydrohalogenation of the free phenol with potassium hydroxide. In the presence of air or peroxides the mode of addition of hydrogen bromide is reversed and cyclization gives benzo-pyran. /3-Keto derivatives ate prepared by a similar ring closure. ... 

A convenient way selectively to introduce a chlorine atom into the methyl group of a methyl ketone has been developed. It involves treatment of the imine, formed from the reaction of the methyl-keto-group with ethanolamine, with Af-chlorosuccinimide (see Part II, Chapter 1, ref. 311 and also refs. 149-151 and 156). Various 3-trifluoromethyl derivatives have been prepared by photolytic addition of trifluoroiodomethane across the A -double-bond. ... 

Reaction of 17/J-acetoxy-la,2oc-epoxy-lj3-methyl-5a-androstan-3-one (224) with acid gave an isomeric mixture of A-nor-2-oxo-steroids (225) carrying a formyl group at C(l). Treatment of this mixture with base provided exclusively the l/ -methyl-A-nor-steroid (226).The 3a-methyl-A-norandrostane derivative (230) has been prepared as shown in Scheme 16, i.e. by oxidative cleavage of ring A of the 3-keto-derivative (227) followed by Dieckmann condensation of the diester (228), and methylation and decarboxylation of (229). - ... 

Thus, refluxing methyl P-D-glucoside two equivalents of tributyltin oxide, [(C4Hg)3Sn]20 and molecular sieves (3 A) in chloroform for 2-3 h followed by treatment with two equivalents of bromine at 0 °C furnishes methyl p-D-3-dehydro-3-ketoglucoside in more than 90% yield. Similarly, methyl p-D-xyloside gives the 3-oxo compound, whereas methyl a-D-glu-coside, a-D-galactoside, a-D-xyloside, and p-L-arabinoside yield 70-80% of the corresponding 4-keto derivatives [734],... 

Since aluminum alkoxides function effectively as catalysts for alcohol exchange in esters, reduction of keto esters by aluminum isopropoxide frequently yields the isopropyl ester of the hydroxy add. Thus the reduction of the cyclopropane derivative XLIV gave the isopropyl ester of the reduced acid (XLV). Similarly the substituted methyl -keto ester (XLVI)" gave upon reduction the isopropyl esters of the stereoisomeric reduced acids (XLVH). 

The synthesis commenced with the known 3-C-methyl derivative 136, available from diacetone glucose via a well described sequence of oxidation, Wittig olefination and reduction. Protection at C6 followed by oxidation gave the 5-keto derivative, which was immediately submitted to Wittig... 

Theander reported that acidic degradation of methyl D-arabino-hexopyranosiduloae and of methyl /3-D-ri )o-hexopyranosid-3-ulose (the 2-and 3-keto derivatives from methyl d-o-glucopyranoside) yield a complex mixture. The proportions of ketosides decrease slightly faster than the parent compounds under the same conditions, but the author doubted that hydrolysis of the glycosidic bond is the primary reaction. 

The synthesis of the morphinans 3a-c and the 10-keto derivatives 4a-b are shown in Scheme 1. The experimental details of the syntheses of these compounds will be reported elsewhere (Neumeyer et al., 1999). The compounds were all prepared from commercially available levorphanol 3d which was converted to the O-methyl ether 6 and A -dealkylated to norlevorphanol methyl ether 7. Alternatively, levorphanol (3d) was directly A-dealkylated to norlevorphanol (8). 

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