TfOH-Catalyzed Intramolecular Annulation of 2-(Aryl)-Phenyl-Substituted p-Quinone Methides under Continuous Flow: Total Syntheses of Selaginpulvilin I and Isoselagintamarlin A

Abstract

In this article, we describe a convenient method to access 9-aryl fluorene derivatives through a TfOH-catalyzed intramolecular 1,6-conjugate arylation of 2-(aryl)-phenyl-substituted p-quinone methides (QMs) under continuous flow using the microreaction technique. This method was found to be very effective for most of the p-QMs, and the corresponding 9-aryl fluorene derivatives were obtained in moderate to excellent yields. Moreover, this protocol was further elaborated to the first total syntheses of selaginpulvilin I and isoselagintamarlin A.

Sequential One‐Pot Process to Construct a Dual C−C Bond: Synthesis of Fluorenes and Total Synthesis of 4‐O‐Demethyl‐nobilone

“…All characterization data, original spectra, etc., provided in the Supporting Information. [1][2][3][4]…”

“…Fluorenes are vital frameworks comprising natural products, [1][2][3][4][5][6] biologically active molecules [2,[7][8][9] and molecules of material science relevance (Figure 1). For example, Selaginpulvilins A-J, a quaternary carbon-containing 9,9-disubstituted-9H-fluoreneskeleton-based natural product, extracted from the Selaginella pulvinata, which displayed a potent phosphodiesterase-4 (PDE4) inhibitors [1,2] and exhibited anti-inflammatory properties [10] (Figure 1).…”

Cu(I)-Catalyzed Three-Component Annulation for the Synthesis of 3-Acyl Imidazo[1, 5-a]Pyridines from 2-Pyridinyl-Substituted p-Quinone Methides, Terminal Alkynes, and TsN3 Using O2 as the Oxygen Source

“…para -Quinone methides ( p -QMs), which have been utilizing fully their unique bisvinylogous enone system, displayed remarkable chemical reactivity as versatile precursors for various organic reactions . Among them, p -QMs exhibited obvious advantages in diverse annulation reactions to form carbocycles/heterocycles, which provided a facile method for constructing large functionalized cyclic molecular libraries with precisely defined stereochemical features from various simple synthons with high step economy, efficiency, and scalability . As one of the important members of p -QM families, 2-pyridinyl-substituted p -QMs, which have a potential nucleophilic pyridine group, might be able to be used as unique precursors for the synthesis of 3-acyl- imidazo­[1,5- a ]­pyridines by reacting with other suitable substrates .…”

1,6-Conjugate addition of in situ generated aryldiazenes to p-quinone methides

“…3–5 The core structures of various naturally occurring compounds of biological importance have been designed and synthesized employing p -QMs. 6,7 Hydrazones (Fig. 1) possess diverse biological and pharmacological properties 8–11 such as anti-malarial, anti-cancer, anti-tubercular, anti-microbial, anti-platelet, anti-inflammatory, cardio protective, analgesic, anti-fungal, anti-viral, anti-convulsant, anti-helmintic, anti-protozoal, anti-trypanosomal and anti-schistosomiasis properties.…”