Chain Walking as a Strategy for Iridium-Catalyzed Migratory Amidation of Alkenyl Alcohols to Access α-Amino Ketones

Abstract

Catalytic carbon–nitrogen bond formation in hydrocarbons is an appealing synthetic tool to access valuable nitrogen-containing compounds. Although a number of synthetic approaches have been developed to construct a bifunctional α-amino carbonyl scaffold in this realm, installation of an amino functionality at the remote and unfunctionalized aliphatic sites remains underdeveloped. Here we present a tandem iridium catalysis that enables the redox-relay amidation of alkenyl alcohols via chain walking and metal-nitrenoid transfer, which eventually offers a new route to various α-amino ketones with excellent regioselectivity. The virtue of this transformation is that an unrefined isomeric mixture of alkenyl alcohols can be utilized as the readily available starting materials to lead to the regioconvergent amidation. Mechanistic investigations revealed that the reaction proceeds via a tandem process involving two key components of redox-relay chain walking and intermolecular nitrenoid transfer with the assistance of hydrogen bonding, thus representing the competence of Ir catalysis for the olefin migratory C–N coupling with high efficiency and exquisite selectivity.

Iridium-Catalyzed Intramolecular β-C–H Alkenylation of Ketones with Alkynes via a Hydride-Transfer Approach

“…Furthermore, aside from the geminal-dimethyl linkage, other quaternary carbon centers ( 3ab–3ae ) are also suitable for this transformation. It is noteworthy that in the absence of the quaternary carbon center, the desired cyclization product ( 3af ) can still be obtained with a simple methylene, albeit in a lower conversion, implying an important role of the Thorpe–Ingold effect in this reaction …”

Transition Metal-Catalyzed Regioselective Direct C–H Amidation: Interplay between Inner- and Outer-Sphere Pathways for Nitrene Cross-Coupling Reactions

“…In this regard, donor groups preinstalled on the substrate are known to direct regiocontrolled C­(sp 3 )–H cyclometalation by capitalizing on the kinetic preference for five-membered metallacycle formation. This strategy has been widely exploited for primary β-C­(sp 3 )–H amidation (Scheme b). , Recently, Chang and co-workers reported a Ir-catalyzed migratory unactivated methylene C–H amination . The amidation at remote γ-methylene sites remains a formidable challenge.…”

“…29,63 Recently, Chang and co-workers reported a Ircatalyzed migratory unactivated methylene C−H amination. 64 The amidation at remote γ-methylene sites remains a formidable challenge.…”

Electrocatalytic synthesis: an environmentally benign alternative for radical-mediated aryl/alkenyl C(sp2)–C(sp3) cross-coupling reactions

“…Recent years have witnessed the rapid development of nickel-catalyzed “chain-walking-type” reductive cross-electrophile coupling for the construction of C(sp 2 )–C(sp 3 ) bonds. 78 In 2020, Mei and co-workers reported an unparalleled synthetic strategy for the synthesis of 1,1-diarylalkanes by merging nickel catalysis and electrochemistry in an undivided cell (Scheme 50). 79 This practical method realized highly regioselective reductive cross-electrophile coupling between aryl halides and alkyl bromides with good to excellent yields.…”