ChemInform Abstract: A Convenient Synthesis of Hetarylethynyl Ketones from Hetarylcarbaldehydes and Acetylene.

Abstract

Interest in ,-acetylenic ketones is mainly due to the fact that the conjugated system of a triple bond and a carbonyl group is present in many natural compounds having biochemical activity [1]. ,-Acetylenic ketones are often used for the synthesis [1, 2] and functionalization [3, 4] of various aromatic and heterocyclic compounds. Thus, a recently found palladium-free cross coupling of ,-acetylenic ketones with pyrroles and indoles allowed an easy introduction of acylethynyl group into a pyrrole ring [5]. The preparation of ,-acetylenic ketones has been achieved mostly by acylation of terminal alkynes [1, 6, 7], metal acetylides [8], or alkynylboronates [9] with acyl and aryl halides. However, these methods are of little use for preparing acetylenic ketones with a terminal triple bond. Such ketones are most often prepared by the oxidation of secondary propargyl alcohols. For this purpose, stoichiometric or excess amounts of the following oxidants have been used: MnO2 [10], hypervalent iodine compounds [11], pyridinium chlorochromate and dichromate [12], or the Swern oxidant (oxalyl chloride in DMSO) [13]. Amongst ,-acetylenic ketones, the hetarylethynyl ketones remain the least available for two basic reasons, namely, the sensitivity of many heterocycles to oxidants [14] and the difficulty of obtaining secondary acetylenic alcohols. The latter are mainly synthesized by the addition of various acetylides to a carbonyl group [15, 16], while the simplest route to secondary propargyl alcohols via the ethynylation of aromatic aldehydes in the presence of KOH (the Favorsky reaction) has been considered ineffective [17] until now. We report here a convenient synthetic method for hetarylethynyl ketones. It is a combination of a novel variant of the Favorsky reaction with a mild and green, atom efficient oxidation of the obtained