Syntheses of 3,4-Disubstituted Pyrroles and Furans via Lewis Acid-Promoted Semipinacol Rearrangement/Alkyne-Ketone Metathesis Reaction of (C)-2-N- or O-((3-Arylpropargyl)methyl)-Tethered 3,5,5-Trimethyl-2,3-epoxycyclohexan-1-ones

Abstract

The synthesis of 2,3-disubstituted pyrroles via TMSOTf-assisted cyclization reaction of 3,5,5-trimethyl-2,3-epoxycyclohexan-1-ones incorporating a (3-arylpropargyltosylamino)methyl tether at the C-2 position is described. The reaction starts with an acid-promoted semipinacol rearrangement to give a ring contraction cyclopentanone moiety bearing an arylpropargylaminoacetyl side chain. A subsequent alkyne-ketone metathesis affords the pyrrole derivatives in good yields. The 3,4-disubstituted furan analogues can also be available from 3,5,5-trimethyl-2,3-epoxycyclohexan-1-ones with a tethered arylpropargyl methyl ether at the C-2 position and BF3·OEt2 under an atmosphere of oxygen.