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Expeditious Synthesis of Enantioenriched Tetrahydropyrans via Chemoselective C−N bond Cleavage of Aza‐Oxa‐Bicyclo[3.2.1]Octanes
Author(s) -
D'Elia Cecilia Sasso,
Goudedranche Sébastien,
Constantieux Thierry,
Bella Marco,
Bonne Damien,
Rodriguez Jean
Publication year - 2017
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201700735
Subject(s) - electrophile , tetrahydropyran , chemistry , octane , nucleophile , bicyclic molecule , bond cleavage , oxocarbenium , cleavage (geology) , domino , yield (engineering) , combinatorial chemistry , stereochemistry , medicinal chemistry , organic chemistry , ring (chemistry) , catalysis , materials science , geotechnical engineering , fracture (geology) , engineering , metallurgy
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 TiCl 4 /Et 3 SiH 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.