Mechanistic Studies on the Reactions of Bis(alkylthio)carbenes with Vinyl Isocyanates

Nucleophilic bis(alkylthio)carbenes demonstrate unique reactivity in their reactions with vinyl isocyanates.When a rapid addition of an excess amount of the oxadiazoline precursor (1) is reacted with vinyl isocyanate (2), a highly functionalized 2-pyridone (3) is produced.In an effort to further understand the mechanistic pathway followed by this reaction, ab initio methods are employed and experimental results support the proposed thermally induced [4+2] pathway of this reaction. This paper is dedicated to A. I. Meyers on the occasion of his 70 th birthday.Due to the ubiquitous nature of partially reduced nitrogen heterocycles in alkaloids, the efficient synthesis of highly functionalized pyridones and pyrrolidones as synthetic intermediates continues to present a challenge in many total syntheses of natural products.These laboratories have demonstrated the versatility of the vinyl isocyanate function for the assembly of nitrogen heterocycles in a number of contexts. 1Various pyridone adducts can be obtained using ester enolates, enamines 2a and benzynes 2b as electron rich, two-carbon reaction partners with vinyl isocyanates.Functionalized pyrrolidone intermediates can be constructed via [4+1] cycloadditions of vinyl isocyanates with 1,1-dipole equivalents such as alkyl isocyanides, 3a dimethoxycarbene, 3b chiral nucleophilic carbenes 3c and bis(alkylthio)carbenes. 4a-c Herein, we report studies on the reaction channel followed in the reaction of bis(propylthio)carbene precursor (1) with isocyanate (2) that produces the highly functionalized 2pyridone (3) (eq.1).