Site-Selective C6-β-Aminoalkylation of Tetrahydroquinolines with N‑Arylsulfonyl Aryl Aziridines in Hexafluoroisopropanol: A Modular Approach to C6-Alkylated Quinolines

TL;DR

This paper introduces a metal-free method to selectively modify tetrahydroquinolines at the C6 position using aziridines in a specific solvent, enabling efficient and practical synthesis of quinolines.

Contribution

A novel metal-free, site-selective C6-β-aminoalkylation method using N-arylsulfonyl aryl aziridines in HFIP.

Findings

The method achieves high yields (up to 89%) and full stereochemical fidelity.

It demonstrates broad functional group tolerance and practical scalability.

Postsynthetic oxidation directly provides C6-alkylated quinolines.

Abstract

We report a metal-free
method for the site-selective C6-β-aminoalkylation
of tetrahydroquinolines using N-arylsulfonyl aziridines
in HFIP at room temperature. HFIP activates aziridines through hydrogen
bonding, promoting a regioselective SN2-type ring opening.
The method features broad functional group tolerance, high yields
(up to 89%), and full stereochemical fidelity with chiral aziridines.
Gram-scale synthesis with solvent recovery highlights its practicality,
while postsynthetic oxidation provides direct access to C6-alkylated
quinolines.

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