A Short Step Conversion of Alkynyl Propargyl Sulfones into Six-Membered Cyclic β-Ketosulfones via an Amine-Induced Novel Ring Closure

Abstract

Alkynyl propargyl sulfones underwent secondary amine-induced cyclization to give six-membered cyclic enaminosulfones, and the products were subjected to acidic hydrolysis to afford the corresponding cyclic -ketosulfones in high yields.

Hydroalkoxylation-Initiated Cascade on Sulfone-Tethered Aryl Alkynols Gives Cyclic and Spiro-Heterocyclic β-Ketosulfones

“…Compounds 8 and 9 are the BACE1 inhibitor and allosteric inhibitor of Hepatitis C NS5B polymerase, respectively (Scheme B). Not surprisingly, various methods for synthesizing cyclic sulfones have been investigated including use of substituted alkynyl sulfones. , Further, methods that give ready access to multiply substituted six-membered cyclic β-ketosulfone derivatives with good stereocontrol are conspicuous by their absence. , Herein we disclose a base-promoted reaction of sulfone-tethered alkynols for the stereoselective synthesis of various β-ketosulfones involving the propargyl sulfone to allene isomerization/intramolecular hydroalkoxylation/retro- oxa -Michael/6- endo - trig Michael addition cascade. This approach is also extended to the acrylate-tethered alkynol sulfones, which gives access to various spirocyclic β-ketosulfonyl benzofuran/isochroman/indolines, and sulfone-tethered bridged bicyclo[3.3.1]­nonanes.…”