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Single point activation of pyridines enables reductive hydroxymethylation

Abstract:
The single point activation of pyridines, using an electron-deficient benzyl group, facilitates the ruthenium-catalysed dearomative functionalisation of a range of electronically diverse pyridine derivatives. This transformation delivers hydroxymethylated piperidines in good yields, allowing rapid access to medicinally relevant small heterocycles. A noteworthy feature of this work is that paraformaldehyde acts as both a hydride donor and an electrophile in the reaction, enabling the use of cheap and readily available feedstock chemicals. Removal of the activating group can be achieved readily, furnishing the free NH compound in only 2 steps. The synthetic utility of the method was illustrated with a synthesis of (±)-Paroxetine.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1039/d0sc05656a

Authors

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Role:
Author
ORCID:
0000-0003-0976-3373
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Role:
Author
ORCID:
0000-0002-9609-3672
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Role:
Author
ORCID:
0000-0003-0378-2047
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Role:
Author
ORCID:
0000-0003-1844-2811
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Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Organic Chemistry
Role:
Author
ORCID:
0000-0001-7088-6626


Publisher:
Royal Society of Chemistry
Journal:
Chemical Science More from this journal
Volume:
12
Pages:
742-746
Publication date:
2020-11-16
Acceptance date:
2020-11-10
DOI:
EISSN:
2041-6539
ISSN:
2041-6520


Language:
English
Keywords:
Pubs id:
1146175
Local pid:
pubs:1146175
Deposit date:
2020-11-20
ARK identifier:

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