Work

Selective Reductions of Complex Pyridines via NTf-Pyridinium Salts

Year: 2026

Type: article

Abstract: Piperidines are widely found in biologically active compounds, and accessing these N-heterocycles from pyridines is a commonly used strategy. However, this approach is challenging when pyridines are embedded in complex structures, such as those found in pharmaceutical compounds. Here, we present a sequential approach to piperidines that commences with a hydride addition to NTf-activated pyridinium salts. In this method, we combined tris(pentafluorophenyl)borane as a catalyst with a silane reducing agent to achieve 4-selective mono-reduction, and then combined it with metal-catalyzed reductions to obtain tetrahydropiperidine and piperidine derivatives. The process operates on a broad range of pyridines with various functional groups and substitution patterns, as well as on pyridine-containing drugs.

Source: Synthesis

DOI: 10.1055/a-2784-2600

Authors: Celena Josephitis, Andrew McNally

Institution: Colorado State University

Language: English

Topic: Advanced Synthetic Organic Chemistry

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences

Awards: A 400MHz NMR Spectrometer, G4646443404