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Biocatalytic Dynamic Kinetic Resolution for the Synthesis of Atropisomeric Biaryl N‐Oxide Lewis Base Catalysts
Author(s) -
Staniland Samantha,
Adams Ralph W.,
McDouall Joseph J. W.,
Maffucci Irene,
Contini Alessandro,
Grainger Damian M.,
Turner Nicholas J.,
Clayden Jonathan
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201605486
Subject(s) - kinetic resolution , chemistry , aldehyde , catalysis , benzaldehyde , enantiomer , atropisomer , pyridine , isoquinoline , oxide , alcohol , organic chemistry , combinatorial chemistry , enantioselective synthesis
Atropisomeric biaryl pyridine and isoquinoline N‐oxides were synthesized enantioselectively by dynamic kinetic resolution (DKR) of rapidly racemizing precursors exhibiting free bond rotation. The DKR was achieved by ketoreductase (KRED) catalyzed reduction of an aldehyde to form a configurationally stable atropisomeric alcohol, with the substantial increase in rotational barrier arising from the loss of a bonding interaction between the N‐oxide and the aldehyde. Use of different KREDs allowed either the M or P enantiomer to be synthesized in excellent enantiopurity. The enantioenriched biaryl N‐oxide compounds catalyze the asymmetric allylation of benzaldehyde derivatives with allyltrichlorosilane.