Format

Send to

Choose Destination
Org Lett. 2018 Mar 2;20(5):1333-1337. doi: 10.1021/acs.orglett.8b00067. Epub 2018 Feb 20.

Enantioselective Synthesis of α-(Hetero)aryl Piperidines through Asymmetric Hydrogenation of Pyridinium Salts and Its Mechanistic Insights.

Author information

1
Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, Ridgefield, Connecticut 06877, United States.
2
Department of Chemistry, University of Pennsylvania , Philadelphia, Pennsylvania 19104, United States.

Abstract

Enantioselective synthesis of α-aryl and α-heteroaryl piperidines is reported. The key step is an iridium-catalyzed asymmetric hydrogenation of substituted N-benzylpyridinium salts. High levels of enantioselectivity up to 99.3:0.7 er were obtained for a range of α-heteroaryl piperidines. DFT calculations support an outersphere dissociative mechanism for the pyridinium reduction. Notably, initial protonation of the final enamine intermediate determines the stereochemical outcome of the transformation rather than hydride reduction of the resultant iminium intermediate.

PMID:
29461064
PMCID:
PMC5835364
DOI:
10.1021/acs.orglett.8b00067
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Chemical Society Icon for PubMed Central
Loading ...
Support Center