Hydroxymethylene ketone

Selective formylation of the 3,20-diketone (1) with ethyl formate gives the 2-hydroxymethylene ketone (2). Subsequent methylation and acidic de-formylation affords the 2a-monomethyl product (4) in 50% yield. 

Bemannelation of ketones.1 This reaction can be effected by reaction of an allylic Grignard reagent such as methallylmagnesium chloride with the silyl ether of a 2-hydroxymethylene ketone as shown by conversion of 1 to 2 in 86% overall yield. 

Bomah and co-workers [99] developed an efficient procedure for the synthesis of ring-A fused [3,2-h]pyrimidines 53 in a steroidal moiety. The novel steroidal pyrimidines were prepared via a solid phase three-component reaction of a 2-hydro-xymethylene-3-keto steroid, an arylaldehyde and ammonium acetate under micro-wave irradiation. This protocol has been applied successfully to the cyclization of bicyclic, monocyclic and acyclic 2-hydroxymethylene ketones with diversely substituted aromatic aldehydes (Scheme 39). 

Miscellaneous.—The 2-hydroxymethylene-ketone (310) forms a reasonably stable crystalline mesomeric complex (311) by reaction with boron trifluoride. Reaction of the complex with methyl-lithium, followed by acid, gave the 2-ethylidene-ketone (312), though in low yield. 

The corresponding 2a-allyl steroids in the androstane series have been obtained similarly by alkylation of the hydroxymethylene ketone with allyl bromide. 

Wittig condensation of the ylide from the phosphonium salt, 19, with the hydroxymethylene ketone, 20, affords the product,... 

Best results are obtained when the reaction is carried out under acidic conditions. The products are isolated in the form of their stable salts 3 with hydrochloric, perchloric or sulfuric acid.256-257 a-Hydroxymethylene ketones do not condense with benzene-1,2-diamine to give benzodiazepines if the carbonyl group is adjacent to an aromatic ring.258... 

In a separate, dry, 1-L, two-necked, round-bottomed flask fitted to a nitrogen bubbler and equipped with a magnetic stirring bar and a septum inlet is added a solution of 12.6 g (60.0 mmol) of 2-(hydroxymethylene)cyclododecanone (Note 4) in 500 mL of anhydrous ether. The stirred ethereal solution of the hydroxymethylene ketone is treated at 22°C with 33 mL of a freshly prepared mixture (1/1, v/v) of chlorotrimethylsilane and triethylamine (Note 5). An immediate reaction takes place with deposition of a white precipitate. The mixture is stirred thoroughly at 22°C for 15 min to insure complete conversion to the silyl enol ether. 

Diazocycloalkanones, from a-(hydroxymethylene)ketones with p-toluenesulfonyl azide, 51, 88... 

XLIV) centers about elaboration of hydroxymethylene ketone (574) into the tricyclic diketone (578). Alkylation of keto nitrile 575 proceeds exclusively cis to the angular methyl groups as does the subsequent reductive methylation. These authors were not able to achieve aldol cycUzation of keto aldehyde 576 and consequently proceeded to enol lactone 577 The addition of a methyl group to 578 could be achieved regioselectively. Subsequently dehydration gave 579 and its endocyclic isomer which were separated chromatographically. 

Figure 8 Isomers of Schiff bases derived from hydroxymethylene ketones (a-c) and formylcamphor (d-f)...

Hydroxymethylene ketones are formed by using formic ester ... 

The synthesis (184) of the starting compound 430 is discussed in Section VIII,E,4. The ketone 430 was condensed with ethyl formate in the presence of NaH to give the hydroxymethylene ketone 431. Treatment of 431 with DDQ and acidic dioxane for 5 min at room temperature furnished the... 

Treatment of a-hydroxymethylene ketones 646 with (triphenylphosphoranylidene)ethenone forms the intermediate ylide 647, which can undergo an intramolecular Wittig reaction to afford 2//-pyran-2-ones (Scheme 151) <1998T2161>. 

Semicarbazide and hydroxymethylene ketones give isomeric carbamides depending on the conditions the more labile carbamide may be converted into the more stable form by the action of heat or acid.159 271-290... 

N. K. Kochetkov and A. N. Nesmeyanov showed that / -chlorovinyl ketones react with hydrazine in ethanolic solution to give high yields of 3-substituted pyrazoles.297 Unlike hydroxymethylene ketones, which by tautomerism give mixtures of isomeric pyrazoles, /3-chloro-vinyl ketones react with phenylhydrazine to give only one isomer, a point which was verified experimentally.340 This can only be explained... 

A simpler and improved synthesis of 120a was reported recently the lithium salt of oc-hydroxymethylene ketones when reacted with the lithiosulfide 116a at —78 °C gave 120 a in 89 % yield O For a recent review on the synthesis of arylthiocyclopropa-nes see Ref. 63b). 

It has recently been reported that (3-(I-phenylthio)cyclopropyl enones 245 were more conveniently prepared from the lithium salt of P-hydroxymethylene ketone and the phenylthiocyclopropyllithium 116a (vida supra, Sect. 4.6.1) upon treatment with Lewis acids (e.g., A1C13, SnCl4, TiCl4, etc.) in CH2C12 or better with refluxing 50 % aqueous trifluoroacetic acid, they were converted to y-ketocyclobutanones such as 246, Eq. (75) 64>. 

Formyl-2-cyclohexenones (e.g. 129) react with 3-methyl-2-pyrrolidino-l-butene (130) to give, after hydrolysis, bicyclic ketols, e.g. 134, which on dehydration with trifluoroace-tic acid gave octaline diones such as 135 (equation 24)67. This type of [3 + 3] carbocyclization requires a molar ratio enamine enalone of 2 1 for optimum results, which is explained by the exchange of the enamine 130 with hydroxymethylene ketone 131 to form pyrrolidinomethylene ketone 132 and 3-methyl-2-butanone. 

Cyclopentannelation. The adducts (3) of <-lithio-a-mcthoxyallcne with the tri-mcthylsilyl ether of a hydroxymethylene ketone undergo cyclization in the presence of BF, etherate to produce a-mcthylcnecyclopenten(jiies (4)."... 

Quintanilla-Licea R, Teuber HJ (2001) Review on reactions of acetylacetaldehyde with aromatic and biogenic amines and indoles-synthesis of heterocycles via hydroxymethylene ketones. Heterocycles 55 1365-1397... 

Reactions of phenylthiocyclopropyl lithium with alkyl halides and epoxides have also been reported to deliver products opened to a variety of carbonyl derivatives jS-(l-Phenylthio)cyclopropyl enones have been prepared by using lithium salts of a-hydroxymethylene ketones as electrophiles and dehydrating with acid (equation 110). Rearrangement to cyclobutanones occurs with trifluoroacetic acid, whereas thermal vinylcyclopropane-cyclopentene expansion sometimes gives mixtures of regioisomers . 

The related a-hydroxymethylene ketones behaved similarly. However, when the reactions are performed in CHCI3, loss of the formyl group followed by a second arylation results in the formation of the a,a-diarylketone. 33 j e deformylation of the a-aryl-a-formylketone was suppressed by performing the reaction in THF instead of CHCI3. Good yields of the mono a-arylketones were then obtained. 

---