Biocatalytic Dynamic Kinetic Resolution for the Synthesis of Atropisomeric Biaryl N-Oxide Lewis Base Catalysts

Samantha Staniland, Ralph W. Adams, Joseph J W McDouall, Irene Maffucci, Alessandro Contini, Damian M. Grainger, Nicholas J. Turner*, Jonathan Clayden

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

29 Citations (Scopus)
274 Downloads (Pure)

Abstract

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.

Original languageEnglish
Pages (from-to)10755-10759
Number of pages5
JournalAngewandte Chemie - International Edition
Volume55
Issue number36
Early online date9 Aug 2016
DOIs
Publication statusPublished - 26 Aug 2016

Keywords

  • atropisomerism
  • biaryls
  • enzymes
  • kinetic resolution
  • organocatalysis

Fingerprint Dive into the research topics of 'Biocatalytic Dynamic Kinetic Resolution for the Synthesis of Atropisomeric Biaryl N-Oxide Lewis Base Catalysts'. Together they form a unique fingerprint.

  • Profiles

    Cite this

    Staniland, S., Adams, R. W., McDouall, J. J. W., Maffucci, I., Contini, A., Grainger, D. M., Turner, N. J., & Clayden, J. (2016). Biocatalytic Dynamic Kinetic Resolution for the Synthesis of Atropisomeric Biaryl N-Oxide Lewis Base Catalysts. Angewandte Chemie - International Edition, 55(36), 10755-10759. https://doi.org/10.1002/anie.201605486