title: Biocatalytic Dynamic Kinetic Resolution for the Synthesis of Atropisomeric Biaryl N-Oxide Lewis Base Catalysts.
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.
authors: School of Chemistry, University of Manchester, Manchester, M13 9PL, UK.
authors: Samantha
authors: S
authors: Staniland
authors: School of Chemistry, University of Manchester, Manchester, M13 9PL, UK.
authors: Ralph W
authors: RW
authors: Adams
authors: School of Chemistry, University of Manchester, Manchester, M13 9PL, UK.
authors: Joseph J W
authors: JJ
authors: McDouall
authors: Università di Milano, Dipartimento Scienze Farmaceutiche-Sezione di Chimica Generale e Organica "Alessandro Marchesini", Università degli Studi di Milano, 20133, Milano, Italy.
authors: Irene
authors: I
authors: Maffucci
authors: Università di Milano, Dipartimento Scienze Farmaceutiche-Sezione di Chimica Generale e Organica "Alessandro Marchesini", Università degli Studi di Milano, 20133, Milano, Italy.
authors: Alessandro
authors: A
authors: Contini
authors: Johnson Matthey Catalysis and Chiral Technologies, Cambridge, CB4 0FP, UK.
authors: Damian M
authors: DM
authors: Grainger
authors: School of Chemistry, University of Manchester, Manchester Institute of Biotechnology, 131 Princess Street, Manchester, M1 7DN, UK. nicholas.turner@manchester.ac.uk.
authors: Nicholas J
authors: NJ
authors: Turner
authors: School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK. j.clayden@bristol.ac.uk.
authors: Jonathan
authors: 0000-0001-5080-9535
authors: J
authors: Clayden
keywords: atropisomerism; biaryls; enzymes; kinetic resolution; organocatalysis