Construction of Oxygen‐ and Nitrogen‐based Heterocycles from p‐Quinone Methides

Abstract

In the last few years, there has been an explosive growth in the area of para-quinone methide (p-QM) chemistry. This boom is actually due to the unique reactivity pattern of p-QMs, and also their remarkable synthetic applications. In fact, p-QMs serve as synthons for unsymmetrical diaryl-and triarylmethanes, and also for the construction of diverse range of carbocycles and heterocycles. In the last few years, a wide range of structurally complex heterocyclic frameworks could be accessed through the synthetic transformations of structurally modified stable p-QMs. Therefore, the main focus of this review article is to cover the recent advancements in the transition-metal, Lewis acid and base-catalyzed/mediated synthetic transformations of the stable p-quinone methides (p-QMs) to oxygen-and nitrogen-containing heterocycles.

Pd(ii)-catalyzed annulation of terminal alkynes with 2-pyridinyl-substituted p-quinone methides: direct access to indolizines

“…Very recently, 2-enynyl pyridine derivatives have been explored as precursors for the synthesis of highly-substituted indolizines by a few research groups 11 including ours (Scheme 1c). 12 While working on the synthesis of carbocycles/heterocycles 13 from p -quinone methides ( p -QMs), 14 we envisioned that 2-pyridinyl-substituted p -QMs could be used as synthons for 1,3-disubstituted indolizines (Scheme 1d). Herein, we report an unprecedented protocol involving a Pd( ii )-catalyzed highly regiospecific intermolecular [3 + 2]-annulation reactions between 2-pyridinyl substituted p -QMs and terminal alkynes to access a variety of 1,3-disubstituted indolizines.…”

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

“…As a result, 9-aryl fluorene core has become an important target in the recent years, and many reports have been appeared in the literature for the synthesis of this core . While exploring the p -quinone methides ( p -QMs) as synthons to access a wide range of natural and unnatural carbocycles, heterocycles, and other triarylmethane derivatives, we envisioned that 2-(aryl)-phenyl-substituted p -QMs could potentially serve as precursors for the construction of fluorene core of selaginpulvilins and their analogues. Herein, we report an acid-catalyzed intramolecular annulation of 2-(aryl)-phenyl-substituted p -QMs, leading to a variety of 9-aryl-substituted fluorene derivatives.…”

Tropylium Salt-Promoted Vinylogous Aza-Michael Addition of Carbamates to para-Quinone Methides: Elaboration to Diastereomerically Pure α,α′-Diarylmethyl Carbamates

“…For example, Lambert and co-workers demonstrated the utility of the tropylium cation as a mediator in the α-cyanation of amines with KCN . Later, Nguyen’s group demonstrated the catalytic utility of the tropylium cation (mostly as a Lewis acid) in several synthetic methodologies, such as acetalization and trans -acetalization reactions, carbonyl–olefin metathesis reactions, retro-Claisen-type reactions, O–H insertion reactions of carboxylic acids with diazo compounds, etc. − In this manuscript, we intend to demonstrate the catalytic utility of tropylium salts in the vinylogous aza-Michael reactions of para -quinone methides ( p -QMs) − to access unsymmetrical α,α′-diarylmethyl amine derivatives. These compounds have been well-recognized in the area of medicinal chemistry, and many α,α′-diarylmethyl amine-based drugs have been already commercialized (Figure ).…”

“…Recently, our research group has explored the inimitable reactivity of p -QMs to access unsymmetrical diaryl- and triarylmethane derivatives, carbocycles, and heterocycles. − While working in this area, we realized that the concept of “carbocation catalysis” has not yet been utilized in vinylogous conjugate addition reactions of p -QMs, although this concept has been well explored in the activation of simple aldehydes. − Therefore, we decided to employ a tropylium salt as a catalyst or promoter for the vinylogous aza-Michael addition of carbamates to p -QMs to obtain α,α′-diarylmethyl carbamate derivatives. We envisioned that the tropylium salt could activate the p -QM, thereby making it more susceptible for nucleophilic attack with the carbamate.…”