Amide acetals, reaction with malonate

Compound 85 was dehydrogenated at 300° over palladium black under reduced pressure to a pyridine derivative 96 which was independently synthesized by the following route. Anisaldehyde (86) was treated with iodine monochloride in acetic acid to give the 3-iodo derivative 87. The Ullmann reaction of 87 in the presence of copper bronze afforded biphenyldialdehyde (88). The Knoevenagel condensation with malonic acid yielded the unsaturated diacid 91. The methyl ester (92) was also prepared alternatively by a condensation of 3-iodoanisaldehyde with malonic acid to give the iodo-cinnamic acid (89), followed by the Ullmann reaction of its methyl ester (90). The cinnamic diester was catalytically hydrogenated and reduced with lithium aluminium hydride to the diol 94. Reaction with phosphoryl chloride afforded an amorphous dichloro derivative (95) which was condensed with 2,6-lutidine in liquid ammonia in the presence of potassium amide to yield pyridine the derivative 96 in 27% yield (53). 

Chiral phosphinous amides have been found to act as catalysts in enantio-selective allylic alkylation. Horoi has reported that the palladium-catalyzed reaction of ( )-l,3-diphenyl-2-propenyl acetate with the sodium enolate of dimethyl malonate in the presence of [PdCl(7i-allyl)]2 and the chiral ligands 45 gave 46 in 51-94% yields and up to 97% ee (Scheme 38). It is notorious that when the reaction is carried out with the chiral phosphinous amide (S)-45a, the product is also of (S) configuration, whereas by using (R)-45b the enantiomeric (R) product is obtained [165]. 

If a C—H bond is acidic enough, it couples with diazonium salts in the presence of a base, most often aqueous sodium acetate.153 The reaction is commonly carried out on compounds of the form Z—CH2—Z, where Z and Z are as defined on p. 464, e.g., P-keto esters, p-keto amides, malonic ester. 

A broad spectrum of hydrogen-containing nucleophiles react with both aromatic and aliphatic isocyanates compounds containing OH groups (H20, alcohols, phenols, oximes, acids), SH groups (H2S, mercaptans), NH groups (NH3, amines, hydrazines, amides, ureas, urethanes), enolizable compounds such as malonic and aceto acetic esters, etc. Some reactions are given in Table 2.5. 

M. Begtrup and C. Pedersen, Reaction of phenyl azide with amides of malonic acids and phenyl-acetic acid, Acta Chem. Scand., 18 (1964) 1333-1336. 

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