Vinylogous carbonic amides

Acylation of the vinylogous pyrrolidine amide of dimedone with acetic anhydride or acetyl chloride led (possibly indirectly) to the carbon acylation product, whereas trichloroacetyl chloride gave rise to products derived from attack of chloride at the oxygenated double bond position in an initial 0-acylation product (401-404). 

If vinylogous imidazole-A-carboxylates (route A) are treated with nucleophiles such as alkoxides or amines, the corresponding vinylogous carbonic esters or amides are obtained. While reaction of the vinylogous imidazole-TV-carboxylate with a thiol (route A) yields the addition product only, that of the corresponding imidazolium compound (route B) leads to the carbonic thioester in a substitution reaction [3]... 

Vinylogous amides, which have an enamine function in conjugation with a carbonyl group, constitute tridentate systems and thus open the possibility of alkylation on carbon, nitrogen, or oxygen. It has been found that the pyrrolidine enamine of acetylacetone gives rise to a carbon mcthylation but an oxygen ethylation product 41). The alkylation of cyclic 1,3-diketone-derived enamines has been studied 41,283). O Alkylation was found in alcohol solvents and predominant C alkylation in nonprotonic solvents. 

Alkylation of enamines with epoxides or acetoxybromoalkanes provided intermediates for cyclic enol ethers (668) and branched chain sugars were obtained by enamine alkylation (669). Sodium enolates of vinylogous amides underwent carbon and nitrogen methylation (570), while vicinal endiamines formed bis-quaternary amonium salts (647). Reactions of enamines with a cyclopropenyl cation gave alkylated imonium products (57/), and 2-benzylidene-3-methylbenzothiazoline was shown to undergo enamine alkylation and acylation (572). A cyclic enamine was alkylated with methylbromoacetate and the product reduced with sodium borohydride to the key intermediate in a synthesis of the quebrachamine skeleton (57i). 

Various l-alkyl-4-(benzotriazol-l-yl)-l,2,3,4-tetrahydroquinolines have been prepared by condensation of V-alkylaniline with two equivalents of an aldehyde and one equivalent of benzotriazole <95JOC(60)7631>. Quinolones 66 were simply prepared in good yield by heating a mixture of the appropriate vinylogous amide 65 and NaHCOj in the presence of a catalytic amount of palladium(II) acetate and triphenylphosphine in DMF under a carbon monoxide atmosphere <96CC2253>. 

Finally, by placing the additional carbonyl in the carboxylic component, a synthesis of pyridinones 131 has been realized [115]. In this case, the nucleophilic carbon is not the one derived from the acid, but the one initially embedded in the starting aldehyde. Moreover, here a vinylogous Knoevenagel is operating, which is clearly favoured over the reaction involving the carbon a to the amide, thanks to the formation of a stable aromatic 6-membered ring. 

In this section we consider peptide analogues containing the amide surrogates 1 to 11 (Scheme 1). These can be isosteric with the amide group in the sense that consecutive a-carbons are separated by three bonds, as in link 1, the (nitrono) peptides, and link 2, the [methyleneamino(hydroxy)] or (TV-hydroxy reduced amide) peptides. They also can be an N-modified amide, as in link 3, the (TV-hydroxy amide) peptides, and link 4, the (V-aminoamide) peptides. Elongation of the peptide unit by one covalent bond has been realized by the introduction of a heteroatom or a methylene into the backbone, as in link 5, the (hydrazide) peptides, link 6, the (amidoxy) peptides, link 7, the (oxomethyleneamino) peptides, link 8, the [(hydroxy)ethyleneamino] peptides, link 9, the (ethyleneamino) peptides, and link 10 the (oxime) peptides. Finally, insertion of an ethylenic bond (two covalent bonds) between the a-carbon and the carbonyl gives rise to link 11, the (but-2-enamide) or (vinylogous amide) peptides. 

The acetyl-substituted complexes, initially prepared by Jager36 by direct synthesis, have served as the basis for all of the work in this area. It has been shown that the acetyl group can be replaced by substitution, especially nitration, where reaction conditions are rather vigorous.39 The acetyl-substituted complexes are not only nucleophilic at carbon, a property exhibited in the above reaction, but they are also nucleophilic at oxygen, being vinylogous amides, and undergo... 

In the great majority of examples, the reactions of substituents on carbon are those to be expected from a basic knowledge of organic chemistry. For example, cyclic amides (adjacent or vinylogous) are readily converted into the ring chloro derivative from which the chlorine atom may be displaced by a number of standard reactions (Scheme 1) <93H(36)2753>. Similar examples are cited elsewhere <85CPB3336, 94TL397). 

The authors proposed that initial bond formation occurs from the less substituted olefin carbon to the a-carbon of the vinylogous amide to yield diradical intermediate 127 (Scheme 32, path A). This diradical can then undergo carbon-nitrogen bond homolysis to give the observed product, 126. However, the formation of 126 is also consistent with the formation of 128 by a straight cycloaddition followed by cycloreversion as outlined in Scheme 32, path B. 

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