Selective Reductions of Complex Pyridines via NTf-Pyridinium Salts

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.

Keywords

Pyridines - Piperidines - Reduction - NTf-pyridinium salts - Dihydropyridines - Tetrahydropyridines - Late-stage functionalization

Publication History

Received: 07 December 2025

Accepted after revision: 08 January 2026

Accepted Manuscript online:
19 January 2026

Article published online:
11 February 2026

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