Efficient and General Synthesis of 5-(Alkoxycarbonyl)methylene-3-oxazolines by Palladium-Catalyzed Oxidative Carbonylation of Prop-2-ynylamides

Abstract

A variety of prop-2-ynylamides have been carbonylated under oxidative conditions to give oxazolines, oxazolines with chelating groups, and bisoxazolines bearing an (alkoxycarbonyl)methylene chain at the 5 position in good yields. The cyclization-alkoxycarbonylation process was carried out in alcoholic media at 50-70 degrees C and under 24 bar pressure of 3:1 carbon monoxide/air in the presence of catalytic amounts of 10% Pd/C or PdI2 in conjunction with KI. Cyclization occurred by anti attack of an oxygen function on the palladium-coordinated triple bond, followed by stereospecific alkoxycarbonylation, strictly resulting in E-stereochemistry. The structures of representative oxazolines and bisoxazolines have been determined by X-ray diffraction analysis.

Synthesis of Functionalized Heterocycles via Oxidative Carbonylation

“…The group of Costa applied PdI 2 -/KI-catalyzed oxidative carbonylation to prop-2-ynylamides under a mixture of CO and air for the synthesis of 5-(alkoxycarbonyl) methylene-3-oxazolines (Scheme 23) [77]. Under similar reaction conditions, 4-yn-1-ones containing different substituents, prop-2-ynyl α-ketoesters, and prop-2-ynyl α-ketoamides underwent heterocyclization-alkoxycarbonylation to give tetrahydrofuran, dioxolane, and oxazoline, dihydropyridinone, and tetrahydropyridinedione derivatives in satisfactory yields [78].…”

Transition-Metal-Catalyzed Reactions in Heterocyclic Synthesis

“…165 Bacchi et al reported the efficient and general synthesis of the 5-(alkoxylcarbonyl)methylene-3-oxazolines 312 by the palladium-catalyzed oxidative carbonylation of the pro-2-ynylamides 311 (Scheme 99). 166 This reaction is initiated by nucleophilic attack of an oxygen atom of an amide group on an alkyne coordinated by palladium(II), forming the vinylpalladium intermediate 313. The insertion of CO into the C-Pd bond of 313, followed by methanolysis of the resulting acylpalladium complex, affords the esters 312 and Pd(0) catalyst.…”

Five‐Membered Heterocycles: 1,3‐Azoles

“…For example, azido imide 227 reacts to give the corresponding imidazolinone 228 (Scheme 10.126) [362]. Propargylamides 231 are transformed into the correspondent 5-carboxymethylene-4,5-dihydrooxazoles 232 in a Pd-catalyzed process in the presence of CO, an alcohol and molecular oxygen (Scheme 10.128) [364].…”