Ru(II)-Catalyzed Switchable C–H Alkylation and Spirocyclization of 2-Arylquinoxalines with Maleimides via ortho-C–H Activation

Abstract

A Ru(II)-catalyzed facile and controllable protocol for C−H alkylation and spirocyclization of 2-arylquinoxalines with maleimides has been achieved under ambient air in high yields. Sequential ortho-C−H activation and C-annulation results in the formation of diverse polyheterocycles containing spiro[indeno[1,2b]quinoxaline-11,3′-pyrrolidine]-2′,5′-diones, which are of potent interest in medicinal chemistry. Mechanistic investigations suggest a reversible cleavage of the ortho-C−H bond in the turnover-limiting step.

Direct C‐2 arylation of quinoxaline with arylhydrazine salts as arylation reagents

“…Furthermore, the desired product 3a could be transform into tetrahydroquinoxaline (5), which was an important intermediate for the cholesterol ester transfer protein (CETP) inhibitor [25]. At the same time, 3a can also be directly transformed into various spiroindenoquinoxalines with antioxidant and cytotoxic activities (6) [26] and antitumor active AEEgens products (7) [27]. Gratifyingly, treatment 3a by acetylation of azaheteroarenes produces compounds with potential inhibitory central nervous system (CNS) and anticonvulsant activity (8) (Scheme 3) [28].…”

Ruthenium-Catalyzed Oxidative Cross-Coupling Reaction of Activated Olefins with Vinyl Boronates for the Synthesis of (E,E)-1,3-Dienes

“…Based on a previous report, a plausible reaction mechanism for the cross-coupling reaction of vinyl boronate with activated olefins is depicted in Scheme . The catalytic cycle is initiated by in situ-generated reactive ruthenium­(II) species A , which further undergoes transmetalation with vinyl boronate ester B to provide an intermediate C .…”

Maleimides in Directing‐Group‐Controlled Transition‐Metal‐Catalyzed Selective C−H Alkylation

“…In 2021, Hajra achieved the Ru(II)‐catalyzed ortho ‐C−H alkylation and sequential ortho ‐C−H alkylation/C‐annulation of 2‐arylquinoxalines with maleimides, affording 3‐(2‐(quinoxalin‐2‐yl)phenyl)succinimides or spiro[indeno[1,2‐ b ]quinoxaline‐11,3′‐pyrrolidine]‐2′,5′‐diones with potential antioxidant and cytotoxic activity (Scheme 47). [48] This offered a controllable protocol rapidly preparing spiro‐indenoquinoxalines as well as other spiro heterocycles.…”