Chiral Tertiary Amine Thiourea-Catalyzed Asymmetric Inverse-Electron-Demand Diels–Alder Reaction of Chromone Heterodienes Using 3-Vinylindoles as Dienophiles

Abstract

A straightforward and efficient protocol for the construction of structurally and biologically interesting chiral flavanoids incorporating three privileged structures, i.e., chromanone, dihydropyran, and indole, has been developed on the basis of chiral bifunctional tertiary amine thiourea-catalyzed asymmetric inverse-electron-demand Diels-Alder reaction of chromone heterodienes and 3-vinylindoles, which were used as dienophiles.

Inverse‐Electron‐Demand Diels–Alder Reactions: Principles and Applications

“…[39] Magnetic nanoparticles are ag ood support owing to their easeo fs eparation by magnets as wella st heir stability and low toxicity. [40] Thereafter, in 2013 and in 2014, Zhu et al [41] and Li et al [42] made further modifications to this thiourea-based catalyst to suit the requirements of their reactions.…”

“…Magnetic nanoparticles are a good support owing to their ease of separation by magnets as well as their stability and low toxicity . Thereafter, in 2013 and in 2014, Zhu et al . and Li et al .…”

Chiral Thioureas—Preparation and Significance in Asymmetric Synthesis and Medicinal Chemistry

“…Various modified derivatives of Takemoto's catalyst were tested in the enantioselective reduction of ketones with borane; a benzyl-substituted catalyst led to the best outcomes [156]. A piperidine derivative showed the optimal performance among diamine-derived catalysts tested in inverse-electrondemand Diels-Alder cycloaddition [157], Mannich reaction of 2-substituted indolin-3-ones [158], and pyrrolidine-substituted thiourea, in conjugated addition of nitroacetates to unsaturated ketoesters DACH-based bisfunctional thiourea organocatalysts containing a tertiary amine function were developed by Takemoto and co-workers (Figure 7). A dimethylamine derivative appeared to be a versatile promoter, active in various asymmetric transformations: Michael reaction of nitroolefins and malonates [136] or 1,3-dicarbonyl compounds [137], active methylene compounds with α,β-unsaturated imides [138,139], aza-Henry [140], Neber reaction (synthesis of azirine derivatives) [141], aldol reaction [142], and others [110][111][112].…”

One‐Pot Synthesis of 3‐(2‐Fluoroalkenyl)indoles

“…Some examples of substituted 3‐vinylindoles have been reported to demonstrate anticancer and antibacterial activities . These molecules have found application as building blocks for the synthesis of a number of significant biologically active compounds: indole alkaloids, carbazole derivatives, β‐carbolines, cyclopentaindoles; chiral 3‐substituted indoles, tryptophan derivatives, bisindolylmethanes, indole‐substituted 1,2,3,4‐tetrahydroquinolines and flavonoids as well as indole‐substituted 1,1‐diarylethanes and 1,1,1‐triarylethanes. In addition the latter have been reported to exhibit impressive cytotoxicity against a number of human cancer cell lines …”