Ruthenium Catalyzed C−H Acylmethylation of N‐Arylphthalazine‐1,4‐diones with α‐Carbonyl Sulfoxonium Ylides: Highway to Diversely Functionalized Phthalazino‐fused Cinnolines

Abstract

A direct ortho‐Csp2‐H acylmethylation of 2‐aryl‐2,3‐dihydrophthalazine‐1,4‐diones with α‐carbonyl sulfoxonium ylides is achieved through a RuII‐catalyzed C−H bond activation process. The protocol featured high functional group tolerance on the two substrates, including aryl‐, heteroaryl‐, and alkyl‐substituted α‐carbonyl sulfoxonium ylides. Thereafter, 2‐(ortho‐acylmethylaryl)‐2,3‐dihydrophthalazine‐1,4‐diones were used as potential starting materials for the expeditious synthesis of 6‐arylphthalazino[2,3‐a]cinnoline‐8,13‐diones and 5‐acyl‐5,6‐dihydrophthalazino[2,3‐a]cinnoline‐8,13‐diones under Lawesson's reagent and BF3⋅OEt2 mediated conditions, respectively. Of these, the BF3⋅OEt2‐mediated cyclization proceeded in DMSO as a solvent and a methylene source via dual C−C and C−N bond formations.

Ruthenium‐catalyzed C−H Functionalization/Annulation ofN‐Aryl Indazoles/Phthalazines with Sulfoxonium Ylides to access Tetracyclic‐fused Cinnolines

“…To our disappoint, N ‐(4‐nitrophenyl) phthalazine‐1,4‐dione failed to deliver the product. In 2019, Sakhuja described a two‐step protocol for the synthesis of 6‐arylphthalazino[2,3‐ a ]cinnolindiones: Ru‐catalyzed coupling of N ‐phenylphthalazine‐diones with sulfoxonium ylides followed by Lawesson's reagent‐promoted cyclization [22] . Different from Sakhuja's work, our method achieved the formation of phthalazino[2,3‐ a ]cinnolindiones in one‐pot .…”

α-Carbonyl sulfoxonium ylides in transition metal-catalyzed C–H activation: a safe carbene precursor and a weak directing group

“…Sakhuja and co-workers 54 disclosed a Ru( ii )-catalyzed strategy for the coupling of 2-arylphthalazine-1,4-dienones 124 with sulfoxonium ylides 2 to furnish acylmethylated products 125 (Scheme 51a). The reaction between 2-arylphthalazine-1,4-dienones and sulfoxonium ylides proceeded via sp 2 C–H activation, carbene formation and protonation to deliver acylmethylated products.…”

Ruthenium-catalyzed (spiro)annulation of N-aryl-2,3-dihydrophthalazine-1,4-diones with quinones to access pentacyclic spiro-indazolones and fused-cinnolines

“…Phthalazine is one such diazaheterocyclic moiety of paramount importance that has displayed an interesting pharmacological profile, and its derivatives have exhibited anti-inflammatory, 5 antitumor, 6 antihypertensive, 7 antimicrobial 8 and anticonvulsant activities. 9 Using the above highlighted DG-aided functionalization notion, powerful methods have been developed in recent times for the annulation of N -phenyl-2,3-dihydrophthalazine-diones with varied coupling partners, including isocyanates, 10 nitroolefins, 11 propargyl alcohols, 12 alkynes, 13 allenes, 14 sulfoxonium ylides 15 and α-diazo compounds 16 via transition-metal catalysis. However, the synthesis of (spiro)annulative products with N -aryl-2,3-dihydrophthalazine-diones has been explored only to a limited extent.…”