Concise Synthesis of Isocoumarins through Rh-Catalyzed Direct Vinylene Annulation: Scope and Mechanistic Insight

Abstract

Transition-metal-catalyzed activation of inert C−H bonds and subsequent C−C bond formation have emerged as powerful synthetic tools for the synthesis of elaborate cyclic molecules. In this report, we introduce an efficient synthetic method of 3,4-unsubstituted isocoumarins adopting an electron-deficient Cp E Rh complex as the catalyst. The use of vinylene carbonate as a vinylene transfer reagent enables the direct construction of isocoumarins from readily available benzoic acids, without any external oxidants as well as bases. The reaction mechanism is evaluated by computational analysis to find an unprecedented "rhodium shift" event within the catalytic cycle.

Rhodium-Catalyzed Directing Group-Assisted Annulation of Arene C—H Bond with Vinylene Carbonate toward Isocoumarins

“…In this reaction, with the aid of a transformable sulfoximine directing group, the construction of C-O and C-C bonds occurs in one step in the presence of rhodium catalyst. Compared to Miura's work, [10] vinylene carbonate is not served as ethyne surrogate in this procedure, which extends…”

“…A proposed reaction mechanism for this transformation is illustrated in Scheme 4. [10] Firstly, 1a coordinates to the [Cp * Rh] 2 ＋ species, which facilitates the cleavage of the ortho-C-H bond of 1a to form a five-membered rhodacycle A. Secondly, the insertion of vinylene carbonate in the Rh-C bond results in a seven-membered intermediate B.…”

“…Intriguingly, the access of nonsubstituted isocoumarins was rarely reported, which was at least partially duing to the lack of catalytic system using ethyne equivalent. Recently, Miura et al [10][11] reported a concise synthesis of isocoumarins whereby Rh-catalyzed direct vinylene annulation (Scheme 2b).…”

Rh(iii)-catalyzed C–H annulation of sulfoxonium ylides with iodonium ylides towards isocoumarins

“…Transition-metal-catalyzed directed group-assisted C–H bond activation has the merit of being able to construct complicated molecules efficiently, leading to rapid progress in the synthetic community over the decades. 9 In this field, the transition metal (Rh, 10 Ru, 11 Pd 12 and others 13 ) catalyzed C–H functionalization of arenes and coupling with sulfoxonium ylides holds great potential to manufacture various heterocycles. Sulfoxonium ylides have been predominantly used as carbonylation reagents 14 or C2 15 synthons in annulation reactions, usually as C4 16 synthons and occasionally as C3 17 synthons.…”

Oxidative [4 + 2] annulation of 1-naphthols with alkynes accelerated by an electron-deficient rhodium(iii) catalysts

“…1a). This catalyst has proved to be highly effective on directed C–H activation reactions, 5–17 having been previously applied, for instance, in the oxidative [4 + 2] annulation of benzoic acids with internal alkynes under ambient conditions (Fig. 1b, top).…”