N-Heterocyclic Carbene-Catalyzed Three-Component Domino Reaction of Alkynyl Aldehydes with Oxindoles

Abstract

A new and stereoselective synthetic approach to spirooxindole 4H-pran-2-one derivatives with three contiguous stereogenic centers has been developed via an NHC-catalyzed three-component domino reaction of alkynyl aldehydes with oxindoles. The reaction proceeds smoothly in good yields with good to high diastereoselectivities. These novel heterocyclic spirooxindoles may provide promising candidates for drug discovery. Additionally, a possible mechanism for the entire reaction sequence is proposed.

Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes

“…193 The reaction conditions differed markedly from those employed by the same research group in their redox-neutral reaction between indolin-3-ones and ynals ( vide supra ). 194 Thus, a triazolium-derived carbene G 20 was employed in the former reaction, while an imidazolium-derived carbene G 7 was employed in the latter.…”

“…193 The authors successfully explored different substitution patterns on both the ynal and oxindole components (Scheme 135). The reaction gives moderate-to-high yields (40–93%) and good diastereoselectivity (up to >95:5 dr).…”

“…In 2014, Enders reported an enantioselective version of the reaction developed previously by Du and Lu 193 between indolin-3-ones and α,β-unsaturated acylazolium intermediates (Scheme 141). 196 The authors subjected α-bromoenals to indolinones in the presence of the chiral aminoindanol-derived triazolium A 4 to afford dihydropyranoindol-2-ones in moderate-to-good yields (60–72%) and excellent ee values (up to 98% ee).…”

Molecular diversity of spirooxindoles. Synthesis and biological activity

“…The diversely functionalized spirodihydropyran-oxindoles 225 have been obtained by using different metal-mediated carbonyl-addition/cyclization reaction sequences under Grubb's ruthenium-based catalysts (Scheme 60) [125]. As can be seen from the literature, MCRs procedures use different catalysts, such as tris(2-hydroxyethyl)amine [137], L-proline [138], sodium stearate [139], [BMIm]BF 4 [140] as catalysts in an alcoholic or aqueous medium for the activation of these processes, as well as non-catalyst and solvent-free conditions [141][142][143].…”

N‐Heterocyclic Carbene‐Catalyzed [3+3] Annulation of Indoline‐2‐thiones with Bromoenals: Synthesis of Indolo[2,3‐b]dihydrothiopyranones

“…[15] Later,t he [3+ +3] annulation of enals,y nals Scheme1.NHC-catalzyed synthesiso fi ndolopyranones and indolothiopyranones. [17] In spite of the higher nucelophilicity of thioenols over enols, [18] the NHC-catlalyzed reactionu sing thiols is rare. [16] Interestingly,L ue tal.…”