Synthesis of C6-Substituted Isoquinolino[1,2-b]quinazolines via Rh(III)-Catalyzed C–H Annulation with Sulfoxonium Ylides

Abstract

We report the synthesis of C6-substituted isoquinolino­[1,2-b]­quinazolinones via rhodium­(III)-catalyzed C–H annulation with sulfoxonium ylides and evaluation of the cytotoxic activity of the scaffold. This C–H activation approach enables the most straightforward and convergent synthesis of C6-substituted isoquinolino­[1,2-b]­quinazolines reported to date. This operationally simple method is compatible with a wide variety of the sulfoxonium ylide and arene C–H activation coupling partners, permitting access to diverse isoquinolino­[1,2-b]­quinazolines. This method shows a high atom economy, generating H2O and dimethyl sulfoxide (DMSO) as by-products. This method is scalable and operates with exquisite N-lactam cyclization selectivity, thus enabling expedient access to new heterocyclic analogues featuring promising cytotoxic properties.

Divergent Construction of Diverse Scaffolds through Catalyst‐Controlled C−H Activation Cascades of Quinazolinones and Cyclopropenones

“…[12c] Besides, through the Rh III -catalyzed cascade, Szostak successfully developed a strategy for the synthesis of isoquinolino [1,2-b]quinazolines from 2-arylquinazolinones and sulfoxonium ylides (Figure 1B). [13] Cyclopropenone, the smallest strained aromatic ring, has been employed as privileged chemical building blocks to construct complicated molecules in the CÀ H activation field. [14] Representative synthetic works included the construction of cyclopentene spiroisoindolinones developed by Wu, [14b] and the synthesis of chalcones reported by Li.…”

Ruthenium(II)-Catalyzed Homocoupling of α-Carbonyl Sulfoxonium Ylides Under Mild Conditions: Methodology Development and Mechanistic DFT Study

“…It was generally proposed that the cyclic product was formed by the first generation of an acylmethylation intermediate in similar cascade reactions. (Chen et al, 2018;Hu et al, 2018aHu et al, ,b, 2019Liang et al, 2018;Shi et al, 2018;Xiao et al, 2018;Xie et al, 2018bXie et al, , 2019Xie H. et al, 2018;Xu et al, 2018;Zhou et al, 2018;Cai et al, 2019;Chen P. et al, 2019;Cui et al, 2019;Huang et al, 2019;Lai et al, 2019;Liu et al, 2019;Luo et al, 2019;Lv et al, 2019;Nie et al, 2019;Shen et al, 2019;Wu C. et al, 2019;Zhang et al, 2019Zhang et al, , 2020Wu et al, 2020). Further transformations from IM6 were explored theoretically to confirm whether the acylmethylation intermediate (IM8) is key in the formation of 2a (Figure 2).…”

Co(III), Rh(III) & Ir(III)‐Catalyzed Direct C−H Alkylation/Alkenylation/Arylation with Carbene Precursors

“…However, sulfoxonium ylides were used as the carbene precursor, the reaction end up with corresponding annulation product in good yield [29b] . Afterward, a series of publications reported by Chen, Wu and Huang groups.…”