2-Mercaptopyridine - anchimerically-assisted activation of thiols, thioates and ketene thioacetals

Abstract

Abstract. The 2-mercaptopyridine reagent is reviewed with particular emphasis on a) recent developments, and b) comparison to alternative and sometimes superior methodologies. The useful application to macrocyclization or carboxyl activation is limited to special cases featuring additional functionalities. More recently, the reagent was utilized for the stereoselective synthesis of substituted β-lactones, β-lactames and carbohydrates. Scheme 1The reaction mechanism was already lined out in Mukaiyama's first report. The reaction is assumed to proceed via thioate coordination of the Grignard reagent to give the reactive intermediate 5, which is further activated by the Lewis acid for attack by the nucleophile. The immediate delivery of the nucleophile to the carbonyl group gives the complex 6, slowing down further attack from nucleophiles. The stability of this complex 114

Synthesis of 3-Aminopyrazinone Mediated by 2-Pyridylthioimidate−ZnCl2 Complexes. Development of an Efficient Route to a Thrombin Inhibitor

“…We were attracted to 2-mercaptopyridine as an activation group based on its successful application in the areas of macrolide formation, peptide coupling, and glycoside syntheses. − Its ability to provide a template effect in the presence of a metal should enhance reactivity. The preparation of thioimidate 27 was accomplished by the addition of 2-mercaptopyridine to chloroimidate 17 , which was generated in situ from pyrazinone 7 with oxalyl chloride in acetonitrile/DMF (Scheme ) .…”