Oxaazabicyclooctene Oxides, Another Type of Bridgehead Nitrones: Diastereoselective Assembly from Acetylene Gas, Ketones, and Hydroxyl Amine

Abstract

Unique bridgehead nitrones, 8-oxa-6-aza­bi­cyclo­[3.2.1]­oct-6-ene 6-oxides, have been assembled diastereoselectively via acetyldihydropyrans, products of one-pot self-organization of two molecules of ketones and two molecules of acetylene, which after oximation undergo acid-catalyzed ring closure. The proposed mechanism includes the enol double-bond protonation, followed by intramolecular cyclization involving the interaction of the carbocation formed with a nitrogen atom. A broad range of substrates tolerate this facile transformation, in which the bridgehead nitrones were isolated in high yields.

Diastereomerically pure rarely functionalized alkenoyl dihydropyrans, 1,6-diketones, and cyclopentanes from acetylene gas and ketones

“…21 2-Acetyl-3,4-dihydropyrans, precursors of both 1,6-diketones and dihydroxycyclopentanes, are easily transformed to bridgehead dihydro-oxadiazines 18 a and bridgehead nitrones. 13 All these examples convincingly confirm the synthetic utility of the reactions disclosed in this work.…”

“…Dihydropyrans 1h – j were prepared from acetylene and 1,5-diketones following the published procedure. 13,16…”

“…2-Acetyl-3,4-dihydropyrans 1 were synthesized following the published procedures from ketones and acetylene. 13 2-Acetyl-3,4-dihydropyrans 1h–j were prepared from 1,5-diketones and acetylene. 13,16 Ethanol was dried with molecular sieves (4 Å, 4–8 mesh).…”

“…13 2-Acetyl-3,4-dihydropyrans 1h–j were prepared from 1,5-diketones and acetylene. 13,16 Ethanol was dried with molecular sieves (4 Å, 4–8 mesh). All other chemicals and solvents are commercially available and were used without further purification.…”

“…In 2009, we discovered KOH/DMSO-promoted diastereoselective self-organization of 7-methylene-6,8-dioxabicyclo[3.2.1]octanes from two molecules of acetylene and two molecules of ketones, 11 which with trace acids rearrange to substituted 2-acetyl-3,4-dihydropyrans 1 . 12 Recently, we have developed a one-pot method for the conversion of the above reactants (acetylene gas and ketones) to 2-acetyl-3,4-dihydropyrans 1 (Scheme 1), 13 which have been employed in this work for the synthesis of the starting acetyldihydropyrans 1a–m .…”