Synthesis and Reactivity of New β-Enamino Acid Derivatives:  A Simple and General Approach to β-Enamino Esters and Thioesters

Abstract

A new strategy has been developed for the synthesis of several β-enamino acid derivatives. N,N‘-Carbonyldiimidazole has been used as C-acylating agent of methyl ketimines, providing a direct and simple route to new β-enamino carbonyl imidazole derivatives 2. These derivatives 2 were cleanly and efficiently transformed into β-enamino esters 4 (X = O) and thioesters 4 (X = S) by reaction with a great variety of alcohols and thiols, including tertiary ones. Alternative and complementary routes to compounds 4 were also investigated. In addition, β-keto esters 6 have been obtained by mild acid hydrolysis of β-enamino esters 4.

A General and Efficient Method for the Preparation of β‐Enamino Ketones and Esters Catalyzed by Indium Tribromide

“…[11] It is therefore not surprising that many synthetic methods have been developed for the preparation of these compounds. These compounds can be synthesized via addition of metallic ester or amide enolates to nitriles, [12] tosylimines [13] and imidoyl halides, [14] via addition of enamines [15] or ketimines [16] to activated carboxylic acid derivatives and the reaction of b-enamino esters with organolithium reagents. [17] Moreover, b-enamino ketones or esters can also be successfully obtained from the direct condensation of 1,3-dicarbonyl compounds with amines.…”

Cyanuric chloride catalysed rapid conversion of β-ketoesters into β-enaminoesters under mild and solvent-free conditions

“…Reaction between ethyl acetoacetate and aniline, in the absence of a catalyst produced only a trace amount of product after 20 h (entry 1) and inferior results were obtained in the presence of solvents ( -11) and it was observed that with just 2 mol% of cyanuric chloride, the reaction was complete in 10 min and an almost quantitative yield of the corresponding β-enaminoester (98%) was obtained (entry 9). It is important to note that when the amount of cyanuric chloride was increased, there was no improvement in the yield or decrease in reaction time (entries [10][11]. With less than 2 mol% of cyanuric chloride, the reaction was incomplete and resulted in a low yield of the product (50-85%) even after grinding the reaction mixture for 1 h. The results presented in Table 2 showed that the methodology is successful for primary, benzylic and aromatic amines.…”

“…Various methods have been reported for the preparation of β-enaminoesters, including addition of an ester or amide enolate to a nitrile [6], tosyl imines [7] and imidoyl halides [8] and via addition of enamines [9], or ketimines [10] to activated carboxylic acid derivatives. These compounds can also be successfully obtained by direct condensation of β-ketoesters with amines [11].…”

Oxazoline N-Oxide Mediated [3+2] Cycloadditions: Application to a Formal Synthesis of a (+)-β-Methylcarbapenem

“…[5] In a more convergent synthesis, a cycloaddition between the γ,δ-unsaturated enamino ester 11, [6] produced by a Blaise condensation [7] between the organozinc reagent 8 and nitrile 10, was also examined. Thus, as in our initial planning, a cycloaddition reaction between dipole 9 and 2-butenenitrile 10 afforded smoothly the expected adduct 7 as the major product of the reaction.…”