Rh(III)-Catalyzed Enaminone-Directed C–H Coupling with Diazodicarbonyls for Skeleton-Divergent Synthesis of Isocoumarins and Naphthalenes

Abstract

Diversity-oriented synthesis is tremendously useful for expanding the explorable chemical space but restricted by the limited available toolbox of skeleton-diversification chemistry. We report herein Rh(III)-catalyzed coupling of enaminones and diazodicarbonyls for skeleton-divergent synthesis of isocoumarins and naphthalenes. The diazodicarbonyl ring size and pH dependence of the skeleton-forming process demonstrates the achievement of both substrate-and reagent-controlled skeletal diversity generation in a single type of system. An intriguing C−C bond cleavage reactivity is critical for enabling facile synthetic access to isocoumarins.

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

“…Of note, oxime and hydrazone compounds are versatile synthetic building blocks, which have been widely applied in transition-metal-catalyzed cross-coupling reactions and radical transformations [36][37][38]. Based on the literature precedents [27] and our previous work [33][34][35], a mechanism for this Rh-catalyzed C-H activation/ annulation reaction was proposed and depicted in Scheme 5. In The final isocoumarin product 3ba can be generated from 1-F by elimination of imine 1-G [39].…”

“…Based on the literature precedents [ 27 ] and our previous work [ 33 – 35 ], a mechanism for this Rh-catalyzed C–H activation/annulation reaction was proposed and depicted in Scheme 5 . In the presence of AgSbF 6 , dimeric [Cp*RhCl 2 ] 2 transforms into the active Rh catalyst.…”

“…During the preparation of manuscript, the group of Li reported a similar Rh(III)-catalyzed [3 + 3] annulation of enaminones with iodonium ylides [32]. Inspired by the collected contributions [26][27][28] and based on our ongoing research in C-H activation [33][34][35], we recently wondered whether it might be possible to couple iodonium ylides with enaminones in a Rh(III)-catalyzed C-H activation/annulation cascade reaction for the rapid construction of isocoumarins (Scheme 1c).…”

“…In 2016, Zhu et al reported the first example of a Rh-catalyzed C–H functionalization of enaminones with alkynes and α-diazo-β-ketoesters to access naphthalenes [ 26 ]. Very recently, the same group developed an efficient Rh(III)-catalyzed C–H cross-coupling of enaminones with diazodicarbonyls for the divergent construction of isocoumarins and naphthalenes [ 27 ]. Moreover, Loh et al disclosed a Rh-catalyzed formal [4 + 2] cycloaddition of enaminones with diazocarbonyls [ 28 ].…”

Catalytic Olefin-Imine Metathesis: Cobalt-Enabled Amidine Olefination with Enaminones

“…We have proposed and demonstrated the use of enaminone as a synthon for C-H bond functionalization reactions. [25][26][27][28][29][30] These synthetic endeavors have led to the discovery of new reactivity patterns for this electronically push-pull structural motif. In an effort to further expand the reactivity profile of enaminone, the C β =C α bond is targeted as a potentially viable reactive site.…”