Assembly of the Hydroxycinnoline Core via Hydrazide-Assisted Rh(III)-Catalyzed C–H Functionalization and Annulation

Abstract

The structural modification of phthalazinones and indazolones has emerged as a pivotal topic in the catalytic C–H functionalization event. Herein we report the hydrazide-assisted rhodium(III)-catalyzed cross-coupling reactions of N-aryl phthalazinones and N-aryl indazolones with vinylene carbonate. This method provides direct access to tetracyclic hydroxycinnolines. Complete site-selectivity and functional group compatibility were observed.

Rh(III)-Catalyzed C–H Functionalization/Annulation of 1-Arylindazolones: Divergent Synthesis of Fused Indazolones and Allyl Indazolones

“…Based on the preliminary mechanistic experiments and previous reported literatures − a plausible catalytic cycle pathway was proposed in Scheme . The active catalyst Cp*Rh­(III) species I was generated by ligand exchange with [Cp*RhCl 2 ] 2 , AgSbF 6 , and additive NaOAc, followed by the formation of the key rhodium complex II with the substrate 1a via a concerted C–H activation process.…”

“…Because of their versatile applications and pharmacological activities, various synthetic methods for functionalized and fused indazolones have been established . Recently, by using Rh­(III), Ir­(I), and Pd­(II) catalysts, indazolones could act as credible directing groups to synthesize indazolone-fused heterocycles in a tandem manner with high sustainability (Scheme ).…”

Advancement of vinylene carbonate as a coupling partner in metal-catalyzed C–H functionalization

“…Alternatively, simple tuning of reaction parameters could also selectively yield the dehydrated product (Scheme 11, top). 51,52 Control experiments showed that only in the presence of a Rh(III) catalyst, the hydroxyl group on 32a was readily eliminated to result in 33a smoothly. Additionally, the AgSbF 6 additive also enabled the synthesis of the vinylation product in a decent yield while the comparatively neutral AgOAc did not induce the dehydration process.…”

“…Alternatively, simple tuning of reaction parameters could also selectively yield the dehydrated product (Scheme 11, top). 51,52…”

Rhodium-catalyzed divergent dehydroxylation/alkenylation of hydroxyisoindolinones with vinylene carbonate

“…Mechanistically, VC also shows an entirely different reaction pathway compared to the existing carbonates, thus resulting in a great number of exquisite organic transformations. Currently, there are three predominant categories of VC transformations: (1) transformations in which VC acts as a vinylation reagent to accomplish C–H [ n +2] endo -cyclization to rapidly construct various carbon- or hetero-cycles such as isocoumarins, 7 isoquinolinones, 8 indoles, 9 quinolines 10 and others 11 (Scheme 1b); (2) transformations in which VC functions as a one-carbon unit for C–H [ n +1] exo -cyclization to deliver heteroarenes via an acylation process 12 (Scheme 1c); and (3) transformations in which VC behaves as an acylmethyl linear synthon or analogue to execute C–H alkylation 13 (Scheme 1d).…”