Faculty, Staff and Student Publications
Language
English
Publication Date
7-5-2023
Journal
Journal of the American Chemical Society
DOI
10.1021/jacs.3c05044
PMID
37345648
PMCID
PMC10326878
PubMedCentral® Posted Date
June 2023
PubMedCentral® Full Text Version
Post-print
Abstract
Piperidines are frequently found in natural products and are of importance to the pharmaceutical industry. A generally useful asymmetric route to enantiomerically enriched 3-substituted piperidines remains elusive. Here we report a cross-coupling approach to enantioenriched 3-piperidines from pyridine- and sp2-hybridized boronic acids. The key step involves a Rh-catalyzed asymmetric reductive Heck reaction of aryl, heteroaryl, or vinyl boronic acids and phenyl pyridine-1(2H)-carboxylate to provide 3-substituted tetrahydropyridines in high yield and excellent enantioselectivity with a wide functional group tolerance. A three-step process involving i) partial reduction of pyridine, ii) Rh-catalyzed asymmetric carbometalation, and then iii) another reduction provides access to a wide variety of enantioenriched 3-piperidines, including clinically used materials such as Preclamol and Niraparib.
Published Open-Access
yes
Recommended Citation
Sourabh Mishra, Sedef Karabiyikoglu, and Stephen P Fletcher, "Catalytic Enantioselective Synthesis of 3-Piperidines From Arylboronic Acids and Pyridine" (2023). Faculty, Staff and Student Publications. 1623.
https://digitalcommons.library.tmc.edu/uthmed_docs/1623