Gold-Catalyzed Oxidative Ring Expansion of 2-Alkynyl-1,2-Dihydropyridines or -quinolines: Highly Efficient Synthesis of Functionalized Azepine or Benzazepine Scaffolds

An expedient and reliable method for accessing reactive alpha-oxo gold carbenes via gold-catalyzed intermolecular oxidation of terminal alkynes has been developed. Significantly, this method offers a safe and economical alternative to the strategies based on diazo substrates. Its synthetic potential is demonstrated by expedient preparation of dihydrofuran-3-ones containing a broad range of functional groups.

A general solution for the synthesis of various oxetan-3-ones is developed. This reaction uses readily available propargylic alcohols as substrates and proceeds without the exclusion of moisture or air ("open flask"). Notably, oxetan-3-one, a highly valuable substrate for drug discovery, can be prepared in one step from propargyl alcohol in a fairly good yield. The facile formation of the strained oxetane ring provides strong support for the intermediacy of alpha-oxo gold carbenes. This safe and efficient generation of gold carbenes via intermolecular alkyne oxidation offers a potentially general entry into alpha-oxo metal carbene chemistry without using hazardous diazo ketones.