2-halogen-substituted pyridinium-N-phenacylides and their cycloiminium and acyclic analogs: 1. Synthesis of the parent salts, their betaine-ylides, and oxazolium analogs

Abstract

This review deals with an important class of multifunctional reagents, namely, 2-halogen-N-phenacyl pyridinium salts 1 capable of forming betaine-ylides 2 (phenacylides) and thus undergoing 1,3-dipolar cycloadditions and various (cyclo)condensations involving the substitution of both α-halogen and keto-methylene groups. The chemistry of salts 1 and betaines 2 is closely related to the chemistry of oxazolo[3,2-a]pyridinium salts 3. This relationship shows itself in the interconversions of ylides 2 to salts 1 or 3 and, vice versa, of salts 1 and 3 to ylides 2 and in the similarity of chemical transformations not involving such interconversions. This similarity (necessarily involving the α-halophenacylide-oxazolium parallel) is rather unusual and can persist after the replacement of the pyridinium fragment by other heterocycles (azolium and azinium rings) or on passing from halogen to other leaving groups (RS, RO, NR2). This similarity is also manifested in nonheterocyclic open-chain salts where the potentially ylidic CH2CO group is attached to the halogen-iminium group or its functional analog with another heteroatom. The review on the synthesis and transformations of salts 1 and 3 and phenacylides 2 is divided into two parts. The present part is devoted to the synthesis of salts 1 and ylides 3 and the interconversions of 1, 2, and 3. It presents a detailed analysis of synthetic routes to salts 1 and their cycloiminium analogs containing α-halogen or a different (S, O, N) α-heteroatom that serves as a leaving group. The specific features of the synthesis of oxygen- and sulfur-containing salts and their ylides are revealed. Rare examples of the synthesis of aliphatic salts and their “phenacylides“ containing the same structural motif and capable of undergoing ring closure to oxazoles are given. Methods for the generation of phenacylides 2 and their analogs from carbenes and imines, as well as by the ring opening reaction of oxazolium salts are considered.