Aldehydes, 1,4-keto synthesis

Optically active a-kytbvxy aldehydes. A synthesis of chiral a-hydroxy aldehydes involves reaction of 1 with methyl hydroxymethoxyacetate to form the methoxycarbonyl aminal 2. The product is treated with a Grignard reagent in the presence of MgCl2 to form the keto aminal 3. A second Grignard reaction with 3 forms an intermediate (a), which is hydrolyzed to 1 and an a-hydroxy aldehyde (4) ... 

The method can be employed when the substrate contains aldehyde, keto, ester and nitro groups but fails with 4-methoxyphenyltriflate although it shouid have some potential for synthesis in the poiycyciic area. 

An important general method of preparing indoles, known as the Fischer Indole synthesis, consists in heating the phenylhydrazone of an aldehyde, ketone or keto-acld in the presence of a catalyst such as zinc chloride, hydrochloric acid or glacial acetic acid. Thus acrtophenone phenylhydrazone (I) gives 2-phenyllndole (I V). The synthesis involves an intramolecular condensation with the elimination of ammonia. The following is a plausible mechanism of the reaction ... 

A new, versatile and selective synthesis of 6- and 7-substituted pteridines was reported by Rosowsky (73JOC2073). /3-Keto sulfoxides, which can be viewed as latent a keto aldehydes, react with (251) to give 6-substituted pterins, and the use of a-keto aldehyde hemithioacetals leads in a regiospecific synthesis to the isomeric 7-substituted pterins (equation 85). 

B I G I N E L L I Pyrlmidone synthesis Pyrfmdone synthesis from urea, an aldehyde and a 0-keto ester... 

One step synthesis o( substrtuted pyridines from a beta keto ester, an aldehyde arid ammonia. 

Alpha amino acids (and aldehydes) synthesis by reaction of an alpha keto add with another amino acid (Herbst-EngeO or by reaction of a keto acid with ammonia tmdef reducing conditions (Knoop-Oe sterling). 

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. 

Teloidine, the basic hydrolytic product of meteloidine, has been synthesised recently under physiological conditions by Schdpf and Arnold, on the lines of the tropinone synthesis, mesotartaric aldehyde (CHOH. CHO)j, being condensed at 25° with aeetonediearboxylic acid bnd methylamine hydrochloride to teloidinone (5-keto-l 2-dihydroxy-tropane) whieh on eatalytic hydrogenation yielded teloidine (1 2 5-trihydroxytropane). 

With respect to the carbonyl substrate, a variety of additional functional groups is tolerated, e.g. ester, ether, halogen. With compounds that contain an ester as well as a keto or aldehyde function, the latter usually reacts preferentially. Due to its mild reaction conditions the Wittig reaction is an important method for the synthesis of sensitive alkenes, as for example highly unsaturated compounds like the carotinoid 17 shown above. 

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