Heterocyclic /?-enaminoesters

Heterocyclic /3-enaminoesters, versatile synthons in heterocyclic synthesis , WamhofT, H., Adv. Heterocycl. Chem., 1985, 3S, 299. 

Enaminones were obtained from lactam acetals by reaction with active methylene compounds610. Heterocyclic / -enaminoesters are synthons in the preparation of condensed systems611. Acylated alkyl aminoisobutyrylmalonates (145) can be converted to 3-oxo-2-pyrrolines (146)612,613. 

It is interesting to note that the reaction of 16 with or /zo-hydroxybenzylide-neacetone 21 is followed by intramolecular addition of a hydroxyl group to the double bond of the dihydropyridine. The final isolated product in this case is the azatricyclic heterocyclic system 22 (Scheme 3.7). Intramolecular addition of a hydroxyl group to a carbon-carbon double bond in the dihydropyridine ring also occurs in the reaction of enaminoester 23 with benzylideneacetone 24 [15] (Scheme 3.8). 

Another interesting reaction is the addition of an enaminoester to phenyl 4-chromone sulphonate, leading to a mixture of fused heterocyclic products in nearly equimolar amounts103 (equation 72). 

Reductive cyclization of aliphatic and aromatic bis-enaminoesters via electrochemical methods takes place on cathode to give heterocyclic derivatives227 (Scheme 146). 

The main interest in the reaction with unsaturated carbonyl compounds lies in the synthesis of heterocycles, mainly pyridines. Simple pyridines can be obtained starting with an alkyl aminocrotonate and acrolein , an acetal-substituted enol ether or benzoylacrylonitriles (equation 52). Pyrrolinones are obtained by SnC -catalysed action of 3-ethoxycarbonylacrylonitriles on enaminoester (equation 53). 

Mechanistically, the authors proposed that 852 was first converted to an enaminoester 854 by the in situ generated Vilsmeier reagent (Scheme 1.230). Nucleophilic addition of this enamine to C(2) of the oxazole would generate the oxazabicyclo[2.2.1]heptane 855, which ring opened to a 3H-pyrrole 856. Subsequent proton transfer in 856 then yielded 853. The authors also noted that direct attack of an enamine on a heterocycle was most interesting. 

Sukach VA, Tkachttk VM, Rusanov EB, Roeschenthtiler G-V, Vovk MV (2012) Heterocyclization of N-(l-chloro-2,2,2-trifluoroethylidene)carbamates with P-enaminoesters - a novel synthetic strategy to functionalized trifluoromethylated pyrimidines. Tetrahedron 68 8408-8415... 

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