A Simple Stereoselective One Pot Conversion of Compounds With a Dimethylaminomethylene Group Into Enol Esters

Abstract

A simple stereoselective synthesis of 2Z and 2Z,1 0 E alkyl 3-acyloxy-2-(2,2-disubstituted ethenyl) aminopropenoates 4 from alkyl 2-(2,2-disubstituted ethenyl)amino-3-dimethylaminopropenoates 1 in 12-91% yield is presented.

Synthesis of Heterocycles from Alkyl 3-(Dimethylamino)propenoates and Related Enaminones

“…Reactions are acid-catalyzed and, most probably, they proceed by an addition-elimination mechanism (Figure 6). 7-12,32,34,35,47-49,52-54,60-62,66-70, 78,80 Namely, in the reaction of propenoates 15a,c with barbituric acid (65a), the intermediate adducts 66a,c have been isolated (Scheme 7). 50 With dinucleophiles, reaction with the ester group can follow, furnishing cyclic products.…”

“…14,42 However, when the reaction is carried out in refluxing acetone in the presence of a large excess of acyl chloride, 3-(acyloxy)-2-[(2,2-disubstituted-ethenyl)amino]propenoates 69a-j are formed in 12-91% yields via the corresponding aldehyde 68 and enol 67 intermediates, followed by acylation with acyl chloride (Scheme 8; Table 13). 80 Furthermore, when 3-(dimethylamino)propenoates 13w,x,z were hydrolyzed with a solution of HCl in ethanol, the corresponding 3-hydroxypropenoates 70a-c were obtained in 27-85% yields. Similarly, hydantoin-derived enamines 18a-c were converted into enols 71a-c in 55-98% yields (Scheme 9).…”

“…Typical reactive N -nucleophiles are primary and secondary aliphatic, aromatic, and heteroaromatic amines, whereas in the C -nucleophile series, treatment with active methylene compounds, such as 1,3-dicarbonyl compounds and their cyclic analogues, indole derivatives, heteroarylacetic acid derivatives, and hydrogen cyanide, gives the substitution products (see sections 5.1.1−5.1.3 and 5.3.1). Reactions are acid-catalyzed and, most probably, they proceed by an addition−elimination mechanism (Figure ). − ,,,,− ,− ,− ,− ,,

6 Dimethylamine substitution reactions of 3-(dimethylamino)propenoates with N - and C -nucleophiles.

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“…Usually, hydrolysis of (dimethylamino)propenoates takes place in the absence of a suitable N - or C -nucleophile. For example, 2-[(2,2-disubstituted-ethenyl)amino]-3-(dimethylamino)propenoates 13b , c , j , o , q , t in the presence of acyl chlorides are converted primarily into N -acylpyrrole-2-carboxylates (see section 5.2.2). , However, when the reaction is carried out in refluxing acetone in the presence of a large excess of acyl chloride, 3-(acyloxy)-2-[(2,2-disubstituted-ethenyl)amino]propenoates 69a − j are formed in 12−91% yields via the corresponding aldehyde 68 and enol 67 intermediates, followed by acylation with acyl chloride (Scheme ; Table ) 8 13 Alkyl 3-Acyloxy-2-[(2,2-disubstituted- ethenyl)amino]propenoates 69 a − j Prepared 80 compdR 1 R 2 R 3 R 4 yield (%) 69a COOEt COOEt Me 4-Me-C 6 H 4 30 69b COMe COMe Me 4-Me-C 6 H 4 23 69c COOBn COMe Me Ph 12 69d COOBn COMe Me 4-Me-C 6 H 4 47 69e COOBn COMe Me 4-Cl-C 6 H 4 17 69f COOEt COOEt Et 4-Me-C 6 H 4 43 69 g COPh COPh Et 4-Me-C 6 H 4 33 69h COOEt pyridin-2-yl Me 4-Cl-C 6 H 4 91 69i COOEt pyridin-2-yl Me Ph 77 69j COOEt pyridin-2-yl Me 4-Me-C 6 H 4 80 …”