Redox‐Neutral Copper(II) Carboxylate Catalyzed α‐Alkynylation of Amines

Abstract

A new strategy for iminium ion isomerization was applied to the direct, redox-neutral α-alkynylation of amines. Cu(II) 2-ethylhexanoate was identified as the optimal catalyst for this three-component coupling reaction of secondary amines, aldehydes and alkynes.

Classical-Reaction-Driven Stereo- and Regioselective C(sp3)-H Functionalization of Aliphatic Amines

“…Similar regioisomeric products were also found in related alkynylation, alkylation and C-P bond formation reactions. [17] However, the use of oxidants and metal-based reagents, which produce toxic chemical wastes, is not desirable, particularly in industry. Therefore, in view of developing an environmentally benign protocol, we started our investigation to design a direct arylation reaction that could occur under metal-and oxidant-free conditions.…”

The Rügheimer–Burrows reaction revisited: facile preparation of 4-alkylisoquinolines and 3,5-dialkylpyridines from (partially) saturated amines

“…5 The pericyclic chemistry of azomethine ylides, generated via amine/aldehyde condensations or otherwise, has been well studied, in particular in regard to [3+2]-cycloadditions. 4 Our group has developed a range of transformations in which an initial condensation of a secondary amine with an aldehyde or a ketone, via the intermediacy of an azomethine ylide, ultimately leads to amine α-functionalization, 6 α,α-difunctionalization, 7 or α,β-difunctionalization. 8,9 In these reactions, azomethine ylides do not engage in pericyclic reaction pathways, but rather serve as precursors to iminium ions or enamines that undergo a range of transformations.…”

Redox-Neutral α-C–H Bond Functionalization of Secondary Amines with Concurrent C–P Bond Formation/N-Alkylation

“…As part of our efforts to develop new amine α-C–H bond functionalization reactions, 12,13 we recently reported amine α-cyanations 12m and α-alkynylations. 12n These redox-neutral 14 transformations combine a reductive N -alkylation with an oxidative α-functionalization and feature azomethine ylides as reactive intermediates (Figure 1).…”

“…12n These redox-neutral 14 transformations combine a reductive N -alkylation with an oxidative α-functionalization and feature azomethine ylides as reactive intermediates (Figure 1). Water is produced as the only byproduct.…”

“…An indirect solution to this problem was developed in the case of the α-cyanation; we have shown that α-aminonitriles corresponding to 8 can equilibrate to the thermodynamically more stable regioisomers 7 . 12m In the α-alkynylation, only minimal isomerization was observed between the propargylic amines corresponding to 7 and 8 . 12n Here, good to excellent ratios of 7/8 were obtained by using relatively bulky and/or electron-deficient aromatic aldehydes (e.g., 2,6-dichlorobenzaldehyde, mesitaldehyde).…”