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Biocatalytic Dynamic Kinetic Resolution for the Synthesis of Atropisomeric Biaryl N‐Oxide Lewis Base Catalysts |
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| Authors: | Dr Samantha Staniland Dr Ralph W Adams Dr Joseph J W McDouall Dr Irene Maffucci Dr Alessandro Contini Dr Damian M Grainger Prof Nicholas J Turner Prof Jonathan Clayden |
| Institution: | 1. School of Chemistry, University of Manchester, Manchester, UK;2. Università di Milano, Dipartimento Scienze Farmaceutiche—Sezione di Chimica Generale e Organica “Alessandro Marchesini”, Università degli Studi di Milano, Milano, Italy;3. Johnson Matthey Catalysis and Chiral Technologies, Cambridge, UK;4. School of Chemistry, University of Manchester, Manchester Institute of Biotechnology, Manchester, UK;5. School of Chemistry, University of Bristol, Bristol, UK |
| 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. |
| Keywords: | atropisomerism biaryls enzymes kinetic resolution organocatalysis |