1,4-Keto aldehyde, preparation

Several 1,4-dicarbonyl compounds are prepared based on this oxidation. Typically, the 1,4-diketone 10 or the 1,4-keto aldehyde 12 can be prepared by the allylation of a ketone[24] or aldehyde[61,62], followed by oxidation. The reaction is a good annulation method for cyclopentenones (11 and 13). Syntheses of pentalenene[78], laurenene[67], descarboxyquadrone[79], muscone (14 R = Me)[80]) and the coriolin intermediate 15[71] have been carried out by using allyl group as the masked methyl ketone (facing page). 

Though the dialdehyde-tropinone synthesis does not succeed when the dialdehyde is replaced by a diketone, Blount and Robinson have shown that 1-methyltropinone (XXXV) can be obtained by the interaction of the keto-aldehyde, laevulinaldehyde. Me. CO. CH. CH. CHO, with methylamine and calcium acetonedicarboxylate, and from this by reduction to 1-methyl- -tropine and benzoylation, 1-methyl tropacocaine (b.p. 210°/15 mm. picrate, m.p. 163-4°) has been prepared. 

Organomanganese reagents have also been used to prepare numerous simple or functionalized ketones in high yields.10 They can be also used to carry out in high yields, at room temperature, various chemoselective 1,2-addition reactions, for example to keto aldehydes.11... 

Another reagent which has found use in pinacolic coupling is prepared from VC13 and zinc dust.181 182 This reagent is selective for aldehydes that can form chelated intermediates, such as /1-formyl amides, x-amido aldehydes, a-phosphinoyl aldehydes,183 and y-keto aldehydes.184 It can be used for both homodimerization and heterodimerization. In the latter case, the more reactive aldehyde is added to an excess of the second aldehyde. Under these conditions, the ketal formed from the chelated aldehyde reacts with the second aldehyde. 

The second synthetic approach to oidiolactone C (61) is summarized in Scheme 20. This route also commences with the ozonolysis of trans-communic acid 180. Now, when this compound was exposed to ozone in excess, keto aldehyde 187 was obtained in 76% yield. The key step in this approach was the y-lactone closure via chemoselective reduction of the lactone moiety on compound 189 through a SN2 mechanism. Compound 189 could be prepared by saponification of the corresponding methyl ester with sodium propanethiolate. Once the primary alcohol is oxidized, the completion of the synthesis of key lactone 103 only requires the allylic oxidation of the C-17 methyl with concomitant closure of the 8-lactone. This conversion was achieved with Se02 in refluxing acetic acid to give 103 in 51% yield. 

Chiral 4,4-dialkyl-l-cyclopentenones.1 The chiral bicyclic lactam 2, derived from levulinic acid and 1, on monoalkylation exhibits slight if any selectivity regardless of the electrophile. However, a second alkylation exhibits high endo-selectivity. This product (3), after reductive cleavage, furnishes a keto aldehyde that is cyclized by base to a chiral 4,4-disubstituted-2-cyclopentenone (4). Either antipode of 4 can be prepared by the sequence of alkylation. 

Cyeloalkenes (8, 483). The last step in a synthesis of flexibilene (2), a 15-membered-ring diterpene, involved cyclization of the keto-aldehyde 1, catalyzed with the active titanium metal prepared by reduction of TiClj with Zn-Cu in DME. A mixture of two cyclized products is formed, in which 2 is the major constituent.1... 

A model system demonstrating the nutritional destruction of lysine in bovine plasma albumin (BPA) by reaction with either a dialdehyde (MA) or a keto-aldehyde (MGA) was studied in relation to reaction rates as affected by pH, temperature, reaction time and carbonyl concentration. The BPA was Fraction V obtained from Schwartz/Mann and had a molecular weight of 69 x 103 with sixty lysine residules/mole, an assayed content of 11.4%. It was dissolved in 0.0200 M phosphate-citrate buffer adjusted to the desired pH. Malonaldehyde was prepared by acid hydrolysis of its bis-(dimethyl acetal). An aqueous solution of pyruvic aldehyde was diluted with distilled water and phosphate-citrate buffer to give an MGA solution of the desired pH (16). 

For reducing ozonides or sterically hindered peroxides, magnesium and methanol proved to be a better and mild reducing agent <2004JOC2851>. Thus, the bicylic ozonide prepared from 1-phenylcyclopentene, which is prone to base-mediated cleavage, was cleanly reduced by Mg/MeOH to the keto-acid with the ketonic methyl ester as a by-product, whereas reduction with zinc and acetic acid affords mainly the keto-aldehyde with the keto-acid as a by-product (Equation 7). 

High-quality albuterol was obtained in good yield from this process. However, several environmental disadvantages were identified. The preparation of the keto aldehyde hydrate (KAH) generated dimethyl sulfide, methyl bromide, and trimethyl-sulfonium bromide (this compound sublimed in the condenser). In addition, reduction of the Schiff base with dimethylsulfide borane, although very attractive in simplifying... 

Tliis reaction can be used to prepare either a 0-ciketone or a 0-keto aldehyde. Synthesis of the cnaminc requires an aldehyde or ketone and a secondary amine (frequently pyrrolidine ). 

Note that A is a 0-keto aldehyde, which can be prepared via procedure XV-5 which requires an enamine of an aldehyde and an acid chloride. 

Stereoselective McMurry coupling. Clive and co-workers1 report that a modified McMurry reagent prepared in DME with C8K and TiCl3 ( 2 1) can effect highly stereoselective coupling of keto aldehydes. Thus the key step in a synthesis... 

The formal synthesis of ( )-catharanthine by Imanishi et al.l09a consists in a new preparation of the pentacyclic ketoamide (269), which has previously been converted into catharanthine by Biichi et a/.123 The critical stage in this synthesis (Scheme 38) was the preparation of the quinuclidine ketone (270) by an intramolecular aldol reaction on the keto-aldehyde derived from the piperidine bis-acetal (271). 

Keto aldehydes are prepared by the allylation of aldehydes. Reaction of 2-p-tolylpropanal (27) with allyl bromide gave 2-p-tolyl-2-methyl-4-pentenol (28) in 63% yield. The oxidation of the terminal... 

Diketones or y-keto aldehydes (95) were prepared from y-acetoxy ketones by saponification of the acetate with aqueous sodium hydroxide, followed by oxidation with PCC (equation 23). 

This synthesis is compatible with several variations. Since acetal groups are stable to the conditions, keto aldehydes can be prepared in this way. The second alkylation can also be carried out with tosylates and with epoxides. 

Acylation of ketones having reactive methylene groups by higher esters has been shown to be an excellent method for preparing /3-diketones (method 203). If the acylating ester is an alkyl formate, then a keto aldehyde is formed (50-80%). The formylation is simply brought about by adding sodium metal to a mixture of the ketone and ester in anhydrous ether. Oftentimes, the product is isolated as the sodium salt of the hydroxymethylene form. The point of attack is unpredictable in unsymmetrical ketones, CHjCOCHjR. ... 

Keto aldehyde 191 (Scheme 2.87) was prepared as a common precursor in the synthesis of a series of isoprenoid pheromones. One of the synthetic options required the selective reduction of a ketone carbonyl in this compound. Under mild conditions of acetalization (weak acid, methanol), only the aldehydic function of 191 was affected to form a mono-protected derivative, 192. Reduction of the keto group in the derivative with sodium borohydride and subsequent removal of the acetal protecting group gave the desired hydroxy aldehyde 193. ... 

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