N‐Heterocyclic Carbene‐Catalyzed Enantioselective Annulation of Indolin‐3‐ones with Bromoenals

Abstract

N-Heterocyclic carbene-catalyzed reactions of indolin-3-ones with 2-bromoenals opened an asymmetric access to 3,4-dihydropyrano[3,2-b]indol-2(5 H)-ones in good yields and with good to excellent enantioselectivities. This protocol tolerates a broad substrate scope. In addition, a possible mechanism for the annulation reaction is presented.

Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes

“…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). Electron-donating or -withdrawing groups on the aromatic ring of the α-bromoenal component are well tolerated, as well as heteroaromatic rings.…”

Revealing the Similarities of α,β‐Unsaturated Iminiums and Acylazoliums in Organocatalysis

“…[14] Using indoline 3-ones as the nucleophiles,s ynthesis of indole-fused dihydropyranones was demonstrated by Lu, Du group and Enders group. [77] Moreover,c yclic 1,2-diketones such as 96 also showed divergent reactivity towards 1 and 2.In2009, Rueping and coworkers reported the highly selective synthesis of bicyclo-[3.2.1]octane-6-aldehydes 97 by the reaction of enals with 96 in moderate to good yields and high ee values (Scheme 21). [78] Thei ntermediate 1 was generated from enals using the catalyst 54 and the reaction followed adomino Michael-aldol pathway to form the bicyclic products.Asimultaneous iminium-enamine activation was the key to success of this domino process.Inthe reaction using 2,adifferent reactivity profile was observed to furnish cyclohexenone-fused dihydropyranones 98.Ren, Yuan and co-workers employed ynals for the generation of 2 using carbene formed from ent-17 a.…”

Stereoselective Synthesis of Hydropyrano[3,2‐b]indoles via Organocatalytic Asymmetric Inverse‐Electron‐Demand Oxa‐Diels–Alder Reaction

“…While several methods exist for constructing the isomeric skeleton, few methods are available to stereoselectively construct chiral hydropyrano[3,2‐ b ]indoles, which is another intriguing combination type of synthetically important indole and hydropyran motifs . In 2014, the Enders group reported NHC‐catalyzed enantioselective [3+3] annulation of indolin‐3‐ones with bromoenals to form chiral dihydropyrano[3,2‐ b ]indol‐2‐ones . Efficient catalytic asymmetric reactions are still needed, especially those using other activation modes based on different types of annulation to generate diverse hydropyrano[3,2‐ b ]indole derivatives.…”