Copper‐Catalyzed Formal [4+2] Cycloaddition of Enoldiazoimides with Sulfur Ylides

Abstract

Enoldiazoimides, a new subclass of enoldiazo compounds, generate enol-substituted carbonyl ylides whose reactions with sulfur ylides enable an unprecedented formal [4+2] cycloaddition. The resulting multifunctionalized indolizidinones, which incorporate sulfur, are formed in good yields under mild reaction conditions. The uniqueness of this transformation stems from the role of the silyl-protected enol, since the corresponding acetyldiazoimide failed to provide any cross-products in metal-catalyzed reactions with sulfur ylides. This copper-catalyzed cycloaddition is initiated with the generation of enol-substituted carbonyl ylides and sulfur ylides from enoldiazoimides and sulfonium salts, respectively, and proceeds through stepwise six-membered ring formation, C-O and C-S bond cleavage, and silyl and acetyl group migration.

Copper‐Catalyzed Formal [4+2] Cycloaddition of Enoldiazoimides with Sulfur Ylides

“…Other tested metal catalysts,a sw ell as alternative solvents and bases,failed to further improve the product yield (see Table S1 in the Supporting Information). [12] Sulfonium salts bearing para-a nd meta-substituted phenyl groups generally performed well in this reaction (5c-j). [11] With the optimized reaction conditions in hand (Table 1, entry 4), we sought to explore the substrate scope of this cycloaddition reaction, the results for which are presented in Table 2and Scheme 2.…”

Catalytic asymmetric cycloaddition reactions of enoldiazo compounds

“…The reaction is considered as a [4+2]-cycloaddition that involves the following steps: C−O bond cleavage, silyl group migration, acetyl group migration, and C−S bond cleavage. 70 The use of acetyldiazoimides did not lead to a cycloaddition product; and this observation indicates the important role of silyl-protected enoldiazoimide 66 in this complex transformation.…”

“…The copper(I)-catalyzed reaction of enol-substituted carbonyl ylides (electrophile) and sulfur ylides (nucleophile) generated in situ from enoldiazoimides 66 and sulfonium salts 67, respectively, provides convenient access to substituted indolizidinones 68 which are not available by other synthetic methods (Scheme 17). 70 The introduction of an asymmetric center to enoldiazoimides leads to chiral indolizidinones, and one representative example was reported. The reaction is considered as a [4+2]-cycloaddition that involves the following steps: C−O bond cleavage, silyl group migration, acetyl group migration, and C−S bond cleavage.…”

Functionalization of Diazo Groups by the Nucleophilic Addition of Two Molecules of a Dimethylsulfonium Ylide to α-Diazo-β-ketoesters/ketones: Synthesis of Highly Functionalized Hydrazones

“…To verify this assessment, we have strived to explore the chemistry between α-diazo-β-ketoesters/ketones and dimethylsulfonium ylides. Noteworthy is the recent success of Doyle et al in utilizing dimethylsulfonium ylides as active nucleophiles, which react with catalytically generated electrophilic carbenes from enol diazoacetates/imides . Our work offers a renewed perspective in visualizing the chemistry of diazo compounds and dimethylsulfonium ylides.…”