Issue 18, 2022

Disarming the alkoxide trap to access a practical FeCl3 system for borrowing-hydrogen N-alkylation

Abstract

Borrowing hydrogen N-alkylation is one of the most valuable transformations in organic synthesis, with high selectivity and atomic economy. The general non-noble metal catalysts for borrowing hydrogen usually have limitations on operational convenience or catalytic efficiency. In particular, the development of practical and mild Fe(III) catalysis is a big challenge due to the alkoxide trap in terms of d-wall issues. Inspired by the theoretical design, utilizing an in situ reaction strategy to overcome the alkoxide trap of Fe(III), we present here a practical in situ ferric chloride and bis-(N-heterocyclic carbene) (bis-NHC) system for the borrowing-hydrogen N-alkylation of amines by alcohols under mild reaction conditions, attributed to the merits of bis-NHC in strong-field ligands, strong σ-donation and π-back-donation, and the trans effect. This system was applied to a wide range of alcohols and amines. Through comprehensive experiments and DFT calculations, the mechanism of the reaction was studied, which highlighted the roles of strong-field ligands, strong σ-donation and π-back-donation, and the trans effect by bis-NHC in ensuring the in situ reduction of Fe(III) to Fe(II) and triggering the borrowing of hydrogen under mild conditions.

Graphical abstract: Disarming the alkoxide trap to access a practical FeCl3 system for borrowing-hydrogen N-alkylation

Supplementary files

Article information

Article type
Research Article
Submitted
23 Mai 2022
Accepted
14 Jul 2022
First published
19 Jul 2022

Org. Chem. Front., 2022,9, 4803-4817

Disarming the alkoxide trap to access a practical FeCl3 system for borrowing-hydrogen N-alkylation

Z. Ye, Z. Yang, C. Yang, M. Huang, X. Xu and Z. Ke, Org. Chem. Front., 2022, 9, 4803 DOI: 10.1039/D2QO00825D

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