Catalytic Conversion of N-Heteroaromatics to Functionalized Arylamines by Merging Hydrogen Transfer and Selective Coupling

Abstract

To date, although tremendous advances have been made in N-heteroaryl C–H functionalization, there remain significant unmet challenges in the deconstruction of extensively applied but poorly reactive N-heteroaromatics to useful frameworks. Here, by a strategy merging hydrogen transfer and selective coupling, we present a ruthenium-catalyzed deconstruction of N-heteroaromatics to functionalized arylamines with 2-aminoaryl methanols. The reaction is achieved via sequential functionalization of the β and α sites of the initially formed N-heteroarenium salts followed by a C–N cleavage, which proceeds with the striking features of broad substrate scope, excellent functional group tolerance, high chemoselectivity and atom efficiency, and suitability for a streamlined synthesis of some biomedical molecules. The strategy utilized will pave the way for further development of catalytic transformations of inert organo systems to functional frameworks.

Merging Annulation with Ring Deconstruction: Synthesis of (E)-3-(2-Acyl-1H-benzo[d]imidazol-4-yl)acrylaldehyde Derivatives via I2/FeCl3-Promoted Dual C(sp3)–H Amination/C–N Bond Cleavage

“…To date, reactions involving quinolines are generally concentrated on the selective functionalization to enhance their functional-group diversity . Owing to their inherent high C–N bond dissociation energy and excellent thermodynamic stability, illustrations for the ring deconstruction of quinolines via C–N bond cleavage are still limited. − Therefore, exploration of the ring-opening reactions of quinolines remains a formidable challenge and meaningful goal.…”

“…In 2018, Trofimov and co-workers also established a novel KOH-catalyzed ring-opening reaction of quinolines with disubstituted electron-deficient acetylenes to afford 2-aryl-3-acylquinoline derivatives via an unprecedented disassembly/assembly/difunctionalization sequence, in which C–N bond cleavage was achieved by generation of key zwitterion intermediates (Scheme b) . Recently, Zhang demonstrated an appealing procedure for the ring deconstruction of quinolines to access arylamines derivatives using ruthenium catalysis, which was realized by initial formation of N -heteroarenium salts, followed by sequential functionalization of the N -heteroaryl β and α sites, and C–N bond cleavage (Scheme c) . These elegant examples inspired us to further explore ring-opening reactions to remodel the core framework of quinolines in order to achieve a molecular library with skeletal diversity.…”

Skeletal remodeling of chalcone-based pyridinium salts to access isoindoline polycycles and their bridged derivatives

“…The pentadienals can undergo further cyclization to generate valuable molecules with increasing complexity and diversity. 6 Although valuable progress has been made, there are still some challenges to be overcome, including the following: (1) the driving force for the deconstruction needs to be further explored. Currently, methods for the ring-opening of pyridinium salts are dominated by N , O - or N , N -ketal formation via nucleophilic attack by an amine or hydroxyl group followed by heterolytic C–N bond cleavage by taking advantage of the instability of the in situ generated aminals.…”

Hydride transfer-initiated synthesis of 3-functionalized quinolines by deconstruction of isoquinoline derivatives

“…12 As a continuous effort in this area, we recently demonstrated a ruthenium-catalyzed hydrogen transfer-mediated deconstruction of the N -quinolinium salts into functionalized arylamines with 2-aminoaryl methanols (Scheme 1a). 13 Alternatively, this work also offers a way to synthesize 3-benzyl quinolines.…”