Synthesis of Succinimide Spiro-Fused Sultams from the Reaction of N-(Phenylsulfonyl)acetamides with Maleimides via C(sp²)–H Activation

Abstract

Presented herein is an effective preparation of succinimide spiro-fused sultams through the coupling reaction of N-(phenylsulfonyl)acetamides with maleimides. It is deduced that this reaction should proceed through a cascade process including Rh(III)-catalyzed C(sp 2 )−H bond cleavage of N-(phenylsulfonyl)acetamide, maleimide double bond insertion into the C−Rh bond, β-hydride elimination, reductive elimination, and intramolecular aza-Michael addition. Notably, this cascade procedure features simultaneous annulation and spirocyclization through traceless fusion of the directing group into target product by using air as an economical oxidant to assist the regeneration of the active Rh(III) catalyst. This new method has several advantages including readily accessible starting materials with broad scope, significantly reduced synthetic steps, redox-neutral conditions, high atom-economy, and sustainability.

C–H activation-initiated spiroannulation reactions and their applications in the synthesis of spirocyclic compounds

“…30 Moreover, the NH unit in N-( phenylsulfonyl)acetamides was viable in assisting the CHA reaction with maleimides to give succinimide spiropyrazolo[1,2-a]pyrazolones (Scheme 37). 31 The formation of the product involves the generation of a five-membered rhodacycle via C-H activation, coordination with maleimide, migratory insertion, isomerization, β-hydride elimination, reductive elimination and aza-Michael addition (Scheme 37).…”

Recent advances in spirocyclization of maleimides via transition-metal catalyzed C–H activation

“…Recently, in 2021, Hu et al reported the Rh-catalyzed spirosultams 76 from the reaction of phenylsulfonylacetamides 75 and maleimide 16 derivatives in the presence of NaOAc in ethylacetate medium at 120 °C (Scheme 15). 19 During the optimization study, several additives such as KOAc, CsOAc, AgOAc, Cs 2 CO 3 , K 3 PO 4 , AcOH and PivOH were screened to find out the best combination of the additives and catalyst. It was observed that NaOAc was the best additive to give a high yield of the products.…”

Recent Advances in the Synthesis of 5‐MemberedN‐Heterocycles via Rhodium Catalysed Cascade Reactions

“…[183i] Fortunately, these barriers were overcame by an elegant transition-metal-catalyzed directing group assisted functionalization of CÀ H bond followed by intramolecular annulation or spirolization using easily accessible starting materials. [183j,k] Expanding the above stratergies Hu and co-workers further realized a novel and efficient synthesis of succinimide spirofused sultams through Rh(III)-catalyzed C(sp 2 )-H bond functionalization followed by [4 + 1] [184]…”

“…Finally, intramolecular aza‐Michael reaction of intermediate IV afforded the product 303 (Scheme 89). [184] …”