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

doi:10.1002/anie.201605486

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

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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 language	English
Pages (from-to)	10755-10759
Number of pages	5
Journal	Angewandte Chemie - International Edition
Volume	55
Issue number	36
Early online date	9 Aug 2016
DOIs	https://doi.org/10.1002/anie.201605486
Publication status	Published - 26 Aug 2016

Keywords

atropisomerism
biaryls
enzymes
kinetic resolution
organocatalysis

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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.",

keywords = "atropisomerism, biaryls, enzymes, kinetic resolution, organocatalysis",

author = "Samantha Staniland and Adams, {Ralph W.} and McDouall, {Joseph J W} and Irene Maffucci and Alessandro Contini and Grainger, {Damian M.} and Turner, {Nicholas J.} and Jonathan Clayden",

year = "2016",

month = aug,

day = "26",

doi = "10.1002/anie.201605486",

language = "English",

volume = "55",

pages = "10755--10759",

journal = "Angewandte Chemie - International Edition",

issn = "1433-7851",

publisher = "Wiley-VCH Verlag",

number = "36",

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TY - JOUR

T1 - Biocatalytic Dynamic Kinetic Resolution for the Synthesis of Atropisomeric Biaryl N-Oxide Lewis Base Catalysts

AU - Staniland, Samantha

AU - Adams, Ralph W.

AU - McDouall, Joseph J W

AU - Maffucci, Irene

AU - Contini, Alessandro

AU - Grainger, Damian M.

AU - Turner, Nicholas J.

AU - Clayden, Jonathan

PY - 2016/8/26

Y1 - 2016/8/26

N2 - 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.

AB - 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.

KW - atropisomerism

KW - biaryls

KW - enzymes

KW - kinetic resolution

KW - organocatalysis

U2 - 10.1002/anie.201605486

DO - 10.1002/anie.201605486

M3 - Article (Academic Journal)

C2 - 27504722

AN - SCOPUS:84983551847

SN - 1433-7851

VL - 55

SP - 10755

EP - 10759

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

IS - 36

ER -

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

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