1- Azabutadienes, reaction with enamines

The reaction with 1-azabutadiene is also unfavorable for other reasons. To begin with, the 4 + 2 cyclization is inherently less exothermic than with 2-azabutadiene (see Exercise 20, p. 123). Furthermore, the enamine product will rapidly undergo side-reactions with adventitious electrophiles. An imine-enamine tautomerism which transforms R-N=CH-CH=CH-CH3 into RNH-CH=CH-CH=CH2 also contributes to lowering the yield. Finally, electron-poor dienophiles may undergo a competing reaction with the nitrogen lone pair. 

Similarly, 1-azabutadienes 303 with an A-alkyl substituent react with enamines 304 to give a range of 3,5-disubstituted pyridines 305 in moderate to good yields (Scheme 153) <1984JOC2691>. 2-Azabutadienes are popular choices for [4 + 2] cycloaddition reactions ab initio calculations are available <1992JOC6736>. Electron-rich 2-azabutadienes react with alkynes to give pyridines, e.g., 306 (Scheme 154) <1982JA1428>. 

Nonracemic l-oxo-3-azabutadienes 19 [( + )- or (-)-menthyl benzoyliminoacetates], bearing chiral auxiliaries in the ester function, react with enamines 18 yielding, after hydrolysis, adducts 2110. The diastereoselectivities obtained for combination of chiral dienes 19 with achiral enamines 18a and 18b are low to moderate. The reaction of chiral enamines 18c and 18d with an achiral diene 19d (R2 = CH3) gives adducts with high diastereoselection (d.r. 92.5 7.5 and d.r. 98 2, respectively). The reaction of a chiral diene with a chiral enamine proceeds, in the case of a matched pair, with virtually complete selectivity for enamine 18c. Adducts 21b and 21 d can be desulferized by reduction with Raney nickel in ethanol10. 

Tetrachloropyrimidine is formed in quantitative yield by the cyclization (with FeCla, at 200 °C) of perchloro-l-cyano-3-azabutadiene (Cl2C=N—CC1=CC1CN), itself formed by successive treatment of cyanoethyl)formamide with phosphorus pentachloride and chlorine. j8-Iminoyl-enamines (222), prepared by the reaction of the appropriate anils with nitriles, condense with ethyl chloroformate and carbon disulphide to give excellent yields of 2-oxo- and 2-thioxo-pyrimidines (223 X = O or S). Aldehydes, acetals, and ketals (but not ketones) also react with these enamines (222) to give 1,2-dihydropyrimidines (224) (70—93%). In similar fashion, malondiamidines condense with a large variety of aromatic aldehydes to give 2-aryl-5-arylmethyl-4,6-diaminopyrimidines. °... 

Raw and Taylor (04TL8607) have also exploited the reactivity of the transient s-cis-2-azabutadiene moiety in a cascade process for the synthesis of 4,5-dihydroazocines (Scheme 40). In this sequence, the strained dihydropyridines 119, formed from the reaction of 118 with an enamine derived from cyclobutanone and various secondary amines in situ, undergo disrotatory [4+2]-electrocyclic reaction to produce the trisubsti-tuted-4,5-dihydroazocines 120. 

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