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Asymmetric Hydrogenation of Cationic Intermediates for the Synthesis of Chiral N , O ‐Acetals
Author(s) -
Sun Yongjie,
Zhao Qingyang,
Wang Heng,
Yang Tilong,
Wen Jialin,
Zhang Xumu
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202002930
Subject(s) - cationic polymerization , asymmetric hydrogenation , chemistry , hydride , chemoselectivity , catalysis , iridium , enantiomer , steric effects , rhodium , catalytic cycle , enantioselective synthesis , photochemistry , combinatorial chemistry , organic chemistry , hydrogen
Abstract For over half a century, transition‐metal‐catalyzed homogeneous hydrogenation has been mainly focused on neutral and readily prepared unsaturated substrates. Although the addition of molecular hydrogen to C=C, C=N, and C=O bonds represents a well‐studied paradigm, the asymmetric hydrogenation of cationic species remains an underdeveloped area. In this study, we were seeking a breakthrough in asymmetric hydrogenation, with cationic intermediates as targets, and thereby anticipating applying this powerful tool to the construction of challenging chiral molecules. Under acidic conditions, both N ‐ or O ‐acetylsalicylamides underwent cyclization to generate cationic intermediates, which were subsequently reduced by an iridium or rhodium hydride complex. The resulting N , O ‐acetals were synthesized with remarkably high enantioselectivity. This catalytic strategy exhibited high efficiency (turnover number of up to 4400) and high chemoselectivity. Mechanistic studies supported the hypothesis that a cationic intermediate was formed in situ and hydrogenated afterwards. A catalytic cycle has been proposed with hydride transfer from the iridium complex to the cationic sp 2 carbon atom being the rate‐determining step. A steric map of the catalyst has been created to illustrate the chiral environment, and a quantitative structure–selectivity relationship analysis showed how enantiomeric induction was achieved in this chemical transformation.