Discovering the role of N-heterocyclic carbene as hydrogen borrowing organocatalyst: metal-free, direct N-alkylation of amines with benzyl alcohols?

Organic Chemistry Frontiers Pub Date: 2022-12-07 DOI: 10.1039/D2QO01522F

Abstract

A highly sustainable, bench-stable, N-heterocyclic carbene based organocatalyst has been demonstrated to impersonate the role of a transition-metal catalyst which had already been proven to be a milestone in the hydrogen borrowing reaction of amines with alcohols. In the present study, an inexpensive, non-toxic and commercially available N-heterocyclic carbene based organocatalyst i.e., 1,3-bis(2,4,6-trimethylphenyl)imidazolinium chloride, has been demonstrated to show the efficient storage of hydrogen (in the form of 2H++ 2e?) generated from alcohol oxidation (dehydrogenation step) temporarily through a SET process which then redelivers the same to the in situ generated imine intermediate (hydrogenation step), subsequently leading to the N-alkylation of amines. The established practical catalytic methodology works efficiently with a wide variety of aromatic and hetero-aromatic amines with high functional group tolerance in good to excellent yields. The protocol is operationally simple and is feasible under metal-free mild reaction conditions. The gram-scale synthesis and the intermolecular cyclization to 2-phenyl quinoline shed further light on the versatility of the developed protocol. Isolation of a radical intermediate trapped with a TEMPO free-radical scavenger together suggest a radical pathway. The SET (single electron transfer) to benzyl alcohol from NHC occurs through the formation of a cation radical intermediate. The hydrogenation–dehydrogenation of in situ generated N-heterocyclic carbene N-alkylation of several substituted amines with various substituted benzyl alcohols.

Graphical abstract: Discovering the role of N-heterocyclic carbene as hydrogen borrowing organocatalyst: metal-free, direct N-alkylation of amines with benzyl alcohols
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