Cu^II/TEMPO‐Catalyzed Enantioselective C(sp³)–H Alkynylation of Tertiary Cyclic Amines through Shono‐Type Oxidation

Abstract

A novel strategy for asymmetric Shono‐type oxidative cross‐coupling has been developed by merging copper catalysis and electrochemistry, affording C1‐alkynylated tetrahydroisoquinolines with good to excellent enantioselectivity. The use of TEMPO as a co‐catalytic redox mediator is crucial not only for oxidizing a tetrahydroisoquinoline to an iminium ion species but also for decreasing the oxidation potential of the reaction. A novel bisoxazoline ligand is also reported.

Dialling‐In New Reactivity into the Shono‐Type Anodic Oxidation Reaction

“…Building upon early results for low diastereoselectivity in the α‐alkoxylation reaction, [58–59] enantioselective Shono‐type cross‐coupling [60] and stereoselective synthesis of heterocycles [61] is rapidly gaining momentum and could be a game‐changing application of electrosynthesis in stereocontrolled synthesis.…”

Organic Electrosynthesis Towards Sustainability: Fundamentals and Greener Methodologies

“…A very common indirect oxidative transformation is the selective conversion of primary alcohols (hydroxyl groups of diols and polyols, e. g. carbohydrates) into carboxylic acids mediated by TEMPOs, which was disclosed by Schäfer in 2003 (Scheme 21a) [116] . Following a similar synthetic approach, benzothiazoles and thiazolopyridines, recurrent heterocycles in drugs and bioactive molecules, have been recently synthesized through a TEMPO‐mediated sulfuration‐cyclization (Scheme 21b), [106] while 1‐substituted tetrahydroisoquinolines have been successfully obtained with high enantioselectivity using, in this case, a Cu(II)/TEMPO system [117] …”

Advances in Asymmetric Organotransition Metal-Catalyzed Electrochemistry

“…Very recently, Mei and co-workers [29] reported the first example of Cu/TEMPO (2,2,6,6-tetramethylpiperidinyl-N-oxyl) co-catalyzed electrochemical enantioselective oxidative cross-coupling between cyclic tertiary amines and terminal alkynes using a novel chiral bisoxazoline ligand in an undivided cell (Scheme 5a). The reaction exhibited high enantioselectivity and broad functional group tolerance.…”