1.5- Dicarbonyls Synthesis

One published synthesis uses nitrile (38) for synthon (36) and the first step is essentially a 1,3-dicarbonyl synthesis. Removal of the cyanide by decarboxylation gives (34). Protection of the ketone is necessary for the condensation but not for the reduction if this is kept to the end after the furan is formed, llynthssis ... 

Michael reactions of this kind work best when they follow a catalytic cycle in which the first formed enolate anion of the product (7) is a strong enough base to regenerate the anion (6) of the starting material. Then only a catalytic amount of base is needed unless a mole is consumed in converting the product into the stable anion (8), as in 1,3-dicarbonyl synthesis (Chapter 19). 

Dihapto 7>ligands, in copper complexes, 2, 174 Dihydride iridium complexes, preparation, 7, 396 Dihydrido clusters, with decarutheniums, 6, 1036 Dihydrobenzofuran, carbene C-H insertions, 10, 193 Dihydrobenzopyran, carbene C-H insertions, 10, 193 ring-closing diene metathesis,... 

The stereoselective conjugate addition of /3-keto-ester anions to substituted cyclopentenones has been reported. Similar anions also add in conjugate fashion to a,/3-unsaturated aldehydes in the presence of a phase-transfer catalyst. Asymmetric induction in the conjugate addition of cyclic /3-keto-esters to enones is achieved by the use of cinchona alkaloids as bases. A further 1,5-dicarbonyl synthesis is achieved by a seven-stage sequence involving two conjugate additions the yields reported in each step are excellent (Scheme 80). ... 

The synthesis of pyrazolcs starting from a hydrazine and a 1,3-dicarbonyl compound is a well established reaction in organic synthesis. If a mono-suhstituted hydrazine is reacted with an unsymmctrically substituted 1,3-dicarbonyl compound, two different pyrazole products which arc regioisomers could he formed (sec figure 10.3-2). 

Woodward tried all these different routes except the one based on the 1,6-dicarbonyl relationship. AU were successful, but he eventually chose the route corresponding to a and c. He discusses this synthesis at length in the 1963 reference. 

If we use the rather unreactive B first we should be able to react one aldehyde at a time. The various dialdehydes are available or can be made by the usual l,n-dicarbonyl routes. Synthesis This is what House did ... 

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

Enolate ions of p dicarbonyl compounds are useful intermediates m organic synthesis We shall see some examples of how they are employed m this way later m the chapter... 

Synthesis and Properties. A number of monomers have been used to prepare PQs and PPQs, including aromatic bis((9-diamines) and tetramines, aromatic bis(a-dicarbonyl) monomers (bisglyoxals), bis(phenyl-a-diketones) and a-ketones, bis(phenyl-a-diketones) containing amide, imide, and ester groups between the a-diketones. Significant problems encountered are that the tetraamines are carcinogenic, difficult to purify, and have poor stabihty, and the bisglyoxals require an arduous synthesis. 

Since the structures of the Gabriel-Isay condensation products of 5,6-diaminopyrimidines with unsymmetrical 1,2-dicarbonyl or a-substituted monocarbonyl compounds are always ambiguous, the synthesis of 6- and 7-substituted pteridines by an unambiguous approach was and still is a necessity and an important challenge. 

The addition of 1,3-dicarbonyl compounds to /3-chloroazoalkenes is the basis of a pyrrole synthesis (Scheme 70a) 81TL1059). Pyrroles are also obtained by the reaction of enamines with azoalkenes (Scheme 70b) (79TL2969,81TL1475), and the copper(II) chloride catalyzed addition of 1,3-dicarbonyl compounds to arylazoalkenes (Scheme 70c) (82JOC684). 

The use of a vinylphosphonium salt as the source of the QQ fragment instead of the more commonly employed 1,2-dicarbonyl substrate is illustrated by the pyrrole synthesis in Scheme 79b (8UOC2570). A particularly interesting feature is the intramolecular Wittig reaction with an amide carbonyl group. A very useful synthesis of pyrroles depends upon the addition of the anion of p-toluenesulfonylmethyl isocyanide (TOSMIC) to a,/3-unsatur-... 

Isoxazoles are susceptible to attack by nucleophiles, the reactions involving displacement of a substituent, addition to the ring, or proton abstraction with subsequent ring-opening. Isoxazolium salts are even more susceptible to attack by a variety of nucleophiles, providing useful applications of the isoxazole nucleus in organic synthesis. Especially useful is the reductive cleavage of isoxazoles, which may be considered as masked 1,3-dicarbonyl compounds or enaminoketones. 

Dicarbonyl compounds pyridazine synthesis from, 3, 45 pyrrole synthesis from, 4, 329 reactions... 

Dicarbonyl compounds pyrylium salt synthesis from, 3, 861... 

K N O R R Pyrazole Synthesis Pyrazole synthesis from a -dicarbonyl compourxi arxi a hydrazine. 

Synthesis of fused cyciopentanones (bicyciotS 3 0] octachones) or of propeltanes from a-dicarbonyl compounds wa the double aktol condensation with etoesters 2... 

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