Ruthenium(II)-Catalyzed Construction of Isocoumarins via Dual C–H/C–C Activation of Sulfoxonium Ylides

Abstract

A ruthenium(II)-catalyzed annulation between two molecules of sulfoxonium ylides is achieved, generating a variety of substituted isocoumarins in reasonable yields. This strategy features dual C−H/C−C activation in one pot and has a wide substrate scope and good functional group tolerance.I socoumarin and its derivatives are important natural lactones, which are generally found in natural products as a basic structure. 1 It was found that compounds with an isocoumarin structure have a certain physiological activity, 2 which are widely used in the treatment of cancer, 3 allergies, 4 sterilization, 5 and other aspects. 6 In addition, they could be used as key synthetic intermediates in drug discovery. 7 Thus, the synthesis of compounds with such a skeleton has attracted great interest. 8 Among the many synthetic methods to access these compounds, the transition-metal-catalyzed C−H activation/annulation cascade reactions of benzoic acid derivatives with coupling partners represent one of the most powerful and straightforward methods to isocoumarins. However, the coupling partners are commonly limited to internal alkynes (Scheme 1a). 9 The use of coupling partners other than internal alkynes will greatly enhance the scope of metal-catalyzed synthesis of isocoumarins.Sulfoxonium ylides are carbene precursors that are easier to prepare and more stable and safer than diazonium compounds. 10 Sulfoxonium ylides have been used as alkylating reagents in a variety of reactions. 11−15 Since the first example of rhodium(III)-catalyzed C−H alkylation of arenes with sulfoxonium ylides was independently discovered by Aïssa 11 and Li, 12 sulfoxonium ylides have been widely used as alkylating reagents in transition-metal-catalyzed C−H functionalization of a range of arenes. 13 Recently, Li's work illuminated the method of synthesizing isocoumarins from Nmethoxybenzamides, using sulfoxonium ylides as coupling partners and rhodium(III) as a catalyst (Scheme 1b). 14 Subsequently, a method for the formation of isocoumarins via ruthenium(II)-catalyzed C−H activation/annulation of benzoic acids and sulfoxonium ylides was reported by Ackermann (Scheme 1c). 15 Inspired by the works of Li and Ackermann, we questioned whether sulfoxonium ylides could be able to serve as both arenes 16 and coupling partners in transition-metal-catalyzed C−H activation. As our ongoing interest in C−H activation 17 and C−C cleavage, 18 herein, we disclose a ruthenium(II)-catalyzed dual C−H/C−C activation of sulfoxonium ylides for the synthesis of isocoumarins (Scheme 1d). 19 We initiated our investigation on the model reaction of sulfoxonium ylide (1a) to optimize various reaction parameters. The results are summarized in Table 1. To our delight, under reaction conditions using [RuCl 2 (p-cymene)] 2 as the catalyst, 2,4,6-trimethylbenzoic acid (MesCO 2 H) being an additive, and Na 3 PO 4 as the base in HFIP at 110 °C under an air atmosphere for 24 h, the desired product (2a) was obtained in 78% yield (entry 1). Investigations on various solvents indicat...

Recent Advances in Metal‐Catalyzed C−H Bond Functionalization Reactions of Sulfoxonium Ylides

“…Nearly at the same time, the same reaction was reported by Cheng and co‐workers under slightly different reaction conditions [51] . Huang et al .…”

“…[50] Nearly at the same time, the same reaction was reported by Cheng and co-workers under slightly different reaction conditions. [51] Huang et al reported a Ru-catalyzed [5 + 1] annulation of 1-(2-aminophenyl)pyrroles with α-carbonyl sulfoxonium ylides for the synthesis of pyrrolo[1,2-a]quinoxaline derivatives (Scheme 47). [52] In 2021, Matsunaga et al described a Ru(II) and chiral carbonic acid catalyzed (4 + 2) annulation of sulfoxonium ylides with sulfoximines for synthesis of a chiral product via a carboxylate assisted mechanism where one enantioselective proton is selectively deprotonated by a chiral carboxylate base (Scheme 48).…”

Rhodium(II)-catalyzed multicomponent assembly of α,α,α-trisubstituted esters via formal insertion of O–C(sp3)–C(sp2) into C–C bonds

“…In the course of developing transition metal-catalyzed deacylative cross-coupling of 1,3-diones with carbene precursors, we unexpectedly observed the α,α,α-trisubstituted ester products by using N,N -dimethylformamide (DMF) as solvent 49 – 52 . Herein we report a multicomponent synthesis of α,α,α-trisubstituted esters from 1,3-diones, diazoesters, and DMF using a rhodium(II) catalyst, in which one-oxygen, one-carbon (sp 3 ), and one carbon (sp 2 ), deriving from 1,3-diones, diazoesters, and DMF, respectively, are inserted into C(CO)−C bonds (Fig.…”

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

“…2012; Gao et al, 2015;Zhou et al, 2015;Chen et al, 2016;Wang et al, 2017Wang et al, , 2018Pan et al, 2018;Xie et al, 2018a;Xie H. et al, 2018), in the current report we present a combined experimental and theoretical study of ruthenium(II)-catalyzed homocoupling of α-carbonyl sulfoxonium ylides, affording a variety of isocoumarin derivatives under mild conditions (Scheme 1C). (Liang et al, 2018;Xu et al, 2018;Huang et al, 2019;Zhou et al, 2019;Wen et al, 2020;Zhu et al, 2020). DFT calculations (Shan et al, 2016(Shan et al, , 2018Yu et al, 2017;Lian et al, 2019;Ling et al, 2019) suggested that the reaction is realized by a formal [3+3] annulation initiated by Ru(II)-catalyzed C-H activation.…”