1417604-27-3Relevant articles and documents
Polymer-supported stereoselective synthesis of (1S,5S)-6-oxa-3,8- diazabicyclo[3.2.1]octanes
Schuetznerova, Eva,Oliver, Allen G.,Zajicek, Jaroslav,Krchnak, Viktor
, p. 3158 - 3165 (2013)
We describe a polymer-supported stereoselective synthesis of the (1S,5S)-6-oxa-3,8-diazabicyclo[3.2.1]octane-bridged scaffold by tandem iminium ion cyclization/nucleophilic addition reactions. A series of resin-bound acyclic intermediates bearing different substituents were prepared, and the scope and limitations of the chemical route leading to the bridged scaffold were evaluated. The Thr-derived bridged scaffold was found to be substantially more stable in acid than the Ser-derived scaffold, which was partially transformed into dihydropyrazinones. Substitution at the iminium-forming nitrogen was critical for acid stability, and the N-arylsulfonamides with electron-withdrawing groups yielded the highest purity of the crude products prepared by acid-mediated cleavage. The acid-labile target compounds were synthesized by nucleophile-mediated cleavage from the esterified Wang resin and cyclization in formic acid. The title compounds were prepared by tandem iminium ion cyclization/nucleophilic addition reactions. The scope and limitations of the chemical route leading to the bridged scaffold were evaluated. The Thr-derived bridged scaffold is substantially more stable in acid than the Ser-derived scaffold, which is partially transformed into dihydropyrazinones. Copyright
