Expeditious Synthesis of Enantioenriched Tetrahydropyrans via Chemoselective C−N bond Cleavage of Aza-Oxa-Bicyclo[3.2.1]Octanes

Cecilia Sasso D 'Elia (1) , Sébastien Goudedranche (1) , Thierry Constantieux (1) , Marco Bella (2) , Damien Bonne (1) , Jean Rodriguez (1)

1 ISM2 - Institut des Sciences Moléculaires de Marseille
2 Dipartimento di Chimica

A rapid synthesis of enantioenriched 2,3,4-trisubstituted tetrahydropyrans in good yields and stereoselectivities is reported. The first step is a domino organocatalytic reaction between ambident electrophilic and 1,4-bis-nucleophilic 1,2-ketoamides and 1,3-bis-electrophilic enals, leading to aza-oxa-bicyclo[3.2.1]octane. Then, the TiCl4/Et3SiH system ensures a chemoselective cleavage of the C−N bond and affords the desired trisubstituted tetrahydropyran in good yield and with conservation of the precursors optical purity. This final synthetic operation includes two consecutive oxocarbenium ion formation and reductions.

Mots clés: Tetrahydropyrans; Azepanes; Organo- catalysis; Multiple bond-forming transformations; Oxocarbenium ions

Domaines: Chimie organique

Cecilia Sasso D 'Elia, Sébastien Goudedranche, Thierry Constantieux, Marco Bella, Damien Bonne, et al.. Expeditious Synthesis of Enantioenriched Tetrahydropyrans via Chemoselective C−N bond Cleavage of Aza-Oxa-Bicyclo[3.2.1]Octanes. Advanced Synthesis and Catalysis, 2017, 359 (20), pp.3638-3641. ⟨10.1002/adsc.201700735⟩. ⟨hal-01687211⟩