Alkenyl Fischer Carbene Complexes and α,β‐Unsaturated Imine Derivatives: Synthesis of Azepines and Mechanistic NMR Studies

Abstract

Abstract4‐Amino‐1‐azadienes 1 react with α,β‐unsaturated Fischer carbene complexes at −40°C to give stereoselectively a variety of substituted 3H‐4,5‐dihydroazepines 3; similarly, 1‐hydroxy‐1‐azadienes (α,β‐unsaturated oximes) 6 afforded the corresponding azepine derivatives 7. Chiral, nonracemic carbene complexes 11 gave azepines 12–13 (d.e. = 40–44%) upon reaction with oxime 6a; the major isomers were obtained in a diastereomerically and enantiomerically pure form (45–50% overall yield) after crystallization. An X‐ray structure of 12a allowed assignment of the absolute stereochemistry. The acid hydrolysis of azepines synthesized provided racemic and enantiomerically pure 1,6‐dicarbonyl compounds (±)‐5, (±)‐9, and (–)‐14, as well as diol (–)‐15. The mechanism of the reaction of 1 and 2 was investigated by multinuclear (1H, 13C, 15N, and 183W) NMR characterization of four intermediates (A, B, C, and D) at low temperature. The experimental sequence of events involves: i) 1,2‐nucleophilic addition of the unsubstituted imine nitrogen of 1 to the metal carbene function (zwitterion A, −60°C), ii) cyclization to the seven‐membered ring with 1,2‐migration of the pentacarbonyl metal (zwitterion B, −40°C), iii) reductive elimination and coordination of the metal to the amine nitrogen (intermediate C, −40°C), and iv) thermal decomplexation and tautomerization (intermediate D and compound 3, above −20°C).