Insights into the Pummerer synthesis of oxazolines

Abstract

A rapid and simple method to access unnatural 2-substituted 5-thio oxazolines has been developed. This methodology is based on a Pummerer reaction followed by an intramolecular nucleophilic substitution, which changes the paradigm for the normal use of a base in Pummerer chemistry. We also provide a useful two-step method for the synthesis of the starting material and a mechanistic proposal based on experimental observations, which contests the previously proposed reaction pathway. The reaction proved to be general, and different substituents, such as alkyl, aryl, alkenyl and functionalized groups, can be used without a significant decrease in efficiency.

Bond-Forming and -Breaking Reactions at Sulfur(IV): Sulfoxides, Sulfonium Salts, Sulfur Ylides, and Sulfinate Salts

“…Another application of the Pummerer reaction was presented by the group of Gamba-Sánchez, accessing heterocycles. 30 They reported the synthesis of oxazolines ( 21 ) from β-amidosulfoxides ( 20 ), using oxalyl chloride (Scheme 5). In this reaction, the initially formed α-chlorosulfides readily undergo cyclization upon addition of aqueous ammonia to afford oxazolines in good to excellent yields.…”

“…Another application of the Pummerer reaction was presented by the group of Gamba-Sánchez, accessing heterocycles . They reported the synthesis of oxazolines ( 21 ) from β-amidosulfoxides ( 20 ), using oxalyl chloride (Scheme ).…”

Electrophilic Chlorine from Chlorosulfonium Salts: A Highly Chemoselective Reduction of Sulfoxides

“…Oxalyl chloride has been used as an activator in Pummerer reactions . In these types of reactions, α‐chlorinated sulfides were observed, demonstrating that they can react with Lewis acids or bases, leading to the formation of thionium ions or nucleophilic substitutions.…”

A New Synthesis of UK-2A Acid Facilitated by a Triple Chloro-Pummerer Activation

“…Such transformations are called chloro-Pummerer reaction and have been rarely reported as conversion of a sulfoxide with thionyl chloride into the corresponding S-chloro analogue and its subsequent rearrangement to an -monochlorinated sulfide. [23][24][25][26] We reasoned that a double chloro-Pummerer transformation of the phenylthiomethyl group of 14 plus a following Pummerer-type activation with phenylsulfenyl chloride elimination could be an efficient method to deliver the desired trichloromethyl derivative 15. Actually, this could be realized in 82% isolated yield.…”