Ru(II)-Catalyzed C–H Hydroxyalkylation and Mitsunobu Cyclization of N-Aryl Phthalazinones

Abstract

Ruthenium(II)-catalyzed C(sp 2 )−H functionalization of N-aryl phthalazinones with a range of aldehydes and activated ketone is described. Initial formation of hydroxyalkylated phthalazinones and subsequent Mitsunobu cyclization provided facile access to biologically relevant indazolophthalazinones. The utility of this method is highlighted by synthetic transformations into a series of potentially bioactive scaffolds.

Direct Integration of Phthalazinone and Succinimide Scaffolds via Rh(III)‐Catalyzed C−H Functionalization

“…In this context, various coupling partners such as alkynes, alkenes, α-diazo esters, and aldehydes have been employed for the CÀ C bond formation reaction (Scheme 1). [10] These synthetic routes allows the direct access to valuable phthalazinonecontaining tetracyclic compounds, i. e., cinnolinophthalazinones and indazolophthalazinones. However, the coupling reaction between N-aryl phthalazinones and maleimides has been still unexplored, although maleimides have been widely employed in the catalytic CÀ H functionalizations.…”

Ir(III)-Catalyzed Dual C–H Activation of 2-Aryl Phthalazinediones and 3-Aryl-2H-benzo[e][1,2,4]thiadiazine-1,1-dioxides for the Construction of Spiro-Fused Cyclic Frameworks

“…In recent years, transition-metal-catalyzed ortho -C–H bond functionalization has become an important tool in organic synthesis for the construction of new C–C and C–N bonds without prefunctionalization of the substrate . In particular, the transition-metal-catalyzed cyclization of N -aryl phthalazinediones or pyridazinones with different coupling partners has been developed for the synthesis of a novel class of heterocyles …”

Rhodium(iii)-catalyzed C–H alkylation of arylhydrophthalazinediones with α-Cl ketones as sp3-carbon alkylated agents

“…11 In 2019 and 2022, the two groups of Sakhuja 12 and Yu 13 demonstrated Ru(II)-catalyzed C-H alkylation from 2-arylphthalazine-1,4-diones and sulfoxonium ylides, respectively (Scheme 1a). In 2020, Kim and coworkers 14 reported a Ru(II)-catalyzed C-H alkylation of 2-arylphthalazine-1,4-diones with a range of aldehydes and activated ketones (Scheme 1b). In the same year, Kim's group 15 Initially, 2-phenyldihydrophthalazinedione (1a, 0.2 mmol) was treated with α-Cl acetophenone (2a, 0.4 mmol), [Cp*RhCl 2 ] 2 (5 mol%), AgSbF 6 (20 mol%) and NaOAc (0.3 mmol, 1.5 eq.)…”

“…On lowering the reaction temperature to 60 °C, 85% of 3aa was produced, while 1a was not completely transformed (Table 1, entry 10 vs. entries 8, 9 and 11). The desired product 3aa was obtained in 96% yield when the reaction time was extended to 36 h ( [13][14][15]. The formation of the desired product 3aa was not detected in the absence of [Cp*RhCl 2 ] 2 (Table 1, entry 16).…”