Nitrogen atom insertion into indenes to access isoquinolines

Abstract

We report a convenient protocol for a nitrogen atom insertion into indenes to afford isoquinolines. The strategy further enables the synthesis of pyridines from cyclopentadienes and a facile access to 15N labelled isoquinolines.

Direct Access to Quinazolines and Pyrimidines from Unprotected Indoles and Pyrroles through Nitrogen Atom Insertion

“…2,5-Diphenylpyrrole 3a was chosen as a model substrate as we hypothesized that stabilizing substituents next to the reactive site might facilitate the overall transformation as unfunctionalized pyrroles are too reactive to reliably assess the reaction efficiency. 41 Indeed, desired pyrimidine 4a was isolated in 47% yield. In contrast, unsubstituted pyrrole 3b and 2,5dimethylpyrrole 3c performed poorly under the optimized reaction conditions yielding pyrimidine 4b and 4c in 28% and 13% 1 H NMR yield, respectively.…”

“…After re-evaluation of the reaction conditions used for the nitrogen atom insertion into unprotected indoles, the best yield was obtained when LiHMDS was used as the only nitrogen atom source in combination with bis­( tert -butylcarbonyloxy)­iodobenzene as the optimal oxidant (for more details, see SI). 2,5-Diphenylpyrrole 3a was chosen as a model substrate as we hypothesized that stabilizing substituents next to the reactive site might facilitate the overall transformation as unfunctionalized pyrroles are too reactive to reliably assess the reaction efficiency . Indeed, desired pyrimidine 4a was isolated in 47% yield.…”

Toward the Generation of 2-Amino-3-Formyl Difunctionalized Chromones via Pd-Enabled Rearrangement Strategy

“…Some classic reactions, such as Favorskii, Wolff, Beckmann, Bayer–Villiger and semipinacol rearrangements, have been widely applied in the ring-contraction or ring-expansion reactions by deletion or insertion of a single atom (C, N or O) into parent skeletons, respectively . Recently, Levin, Sarpong, Morandi, Lu, Antonchick, Wei, et al, accomplished the elegant transfigurations of n-member ring to (n-1)- or (n+1)-member ring through skeletal editing technologies (Figure b). These strategies would enable the rapid mutation of skeletons without laborious multistep synthesis, thus providing powerful tools for synthetic science.…”

Late-Stage Molecular Editing Enabled by Ketone Chain-Walking Isomerization

“…Given our group’s interest in reversible catalytic reactions , and molecular editing processes, we sought to develop such a process. Cognizant of the challenges of achieving this through transition-metal catalysis, we looked for a mechanistically distinct approach to perform the desired transformation.…”