3.18 The Ramberg–Bäcklund Rearrangement and the Eschenmoser Coupling Reaction

Autocatalysis in Eschenmoser Coupling Reactions

“…The Eschenmoser coupling reaction (ECR) [1] of thioamides with electrophiles has been exploited in the past decades to synthesize numerous vinylogous amides and urethanes. [2][3][4] The mechanism involves the formation of an α-thioiminium salt (Scheme 1). [5,6] The transformation of the α-thioiminium into the product likely proceeds via a thiirane intermediate, as indirect evidence suggests.…”

“…[5,6] The transformation of the α-thioiminium into the product likely proceeds via a thiirane intermediate, as indirect evidence suggests. [7][8][9] The rate and yield of the ECR increase in the presence of thiophilic P(III) compounds, [2][3][4] which abstract the sulfur atom from the thiirane intermediates, leading to the formation of product alkenes and thiophosphates or phosphine-sulfides. [10][11][12] The ECR between 3-bromooxindole (1) and thiobenzamide (2) proceeds efficiently even without any thiophilic agent or base.…”

Coupling of acceptor-substituted diazo compounds and tertiary thioamides: synthesis of enamino carbonyl compounds and their pharmacological evaluation

“…2,7,10 Traditionally exocyclic enamino carbonyl synthesis is achieved by the imino ester approach or the Eschenmoser coupling reaction. 2,3,11,12 New strategies, such as involving rhodium azavinylcarbenes and isatins, have been reported that complement the imino ester approach and the Eschenmoser coupling reaction. 13 However, they all have limitations.…”

Copper-Catalyzed Coupling of Thioamides and Donor/Acceptor-Substituted Carbenoids: Synthesis of Enamino Esters and Enaminones

“…3,7,8 Because of this importance, various methods are available for enamino ester and enaminone synthesis 2,9−19 and new methods are constantly pursued. 20−27 Exocyclic enamino esters and enaminones are generally prepared by the Eschenmoser sulfide contraction reaction (ESR) 7,28−30 or the imino ester (imidate) approach. 28,31−33 Both methods complement each other.…”

“…Enamino esters and enaminones are important synthetic intermediates. − They have been used in the synthesis of a number of natural products and pharmaceutically active compounds. ,, Because of this importance, various methods are available for enamino ester and enaminone synthesis ,− and new methods are constantly pursued. − Exocyclic enamino esters and enaminones are generally prepared by the Eschenmoser sulfide contraction reaction (ESR) ,− or the imino ester (imidate) approach. ,− Both methods complement each other. In the ESR, a thioamide is the nucleophile, while in the imidate approach, an amide is converted into an electrophile.…”