Generation and Application of o‐Quinone Methides Bearing Various Substituents on the Benzene Ring

Abstract

o-Quinone methides (o-QMs) are highly reactive, short-lived intermediates, which have potential synthetic applicability. However, few studies on the generation of o-QMs bearing an electronwithdrawing group have been reported. Herein we present a general method for the generation of oQMs, particularly those substituted with an electrophilic substituent, from new precursors, 4H-1,2-benzoxazines 2. We have also studied systematically the Diels-Alder reactions of o-QMs with various dienophiles, such as vinyl ethers, enamines and imines. The reactions provide a versatile route to substituted chromans, phenols and 3,4-dihydro-2H-benzo[e]-A C H T U N G T R E N N U N G [1,3]oxazines (3,4-dihydro-1,3-benzoxazines). Furthermore, we applied the new method to the derivatization of some natural products.

Antineoplastic Isoflavonoids Derived from Intermediate ortho‐Quinone Methides Generated from Mannich Bases

“…The in situ generation of ortho -quinone methides from phenolic Mannich bases,[11] hydroxybenzyl alcohol derivatives,[12] and oxygen-contain heterocycles[13] provided chromane derivatives in hetero-Diels-Alder reaction but the generation of ortho -quinone methides in a chromone platform was without precedent. It was unclear at the outset of this work if the reactive 1,4-benzopyrone functionality in isoflavonoids would accommodate a transitory ortho -quinone methides and trap dieneophiles without competitive, interfering reactions.…”

Catalytic asymmetric tandem Friedel–Crafts alkylation/Michael addition reaction for the synthesis of highly functionalized chromans

“…The benzopyran framework has attracted considerable attention because of the importance of chromans and their biological properties. Numerous synthetic routes have been reported over the past few decades [21–32]. Chiral indolyl(nitro)chromans have been successfully synthesized in our previous study [33].…”

The Construction of Polysubstituted Aromatic Core Derivatives via a Cycloaddition/Oxidative Aromatization Sequence from Quinone and β‐Enamino Esters

“…[1] Furthermore, b-enamino esters are employed as key starting reagents for the synthesis of substituted pyra-Quinones represent one of the most widely distributed structural classes in nature, [17] and compounds belonging to this class can be found in a large number of important pharmacophores [18] associated with anti-cancer, antibacterial, antimalarial, fungicidal, and antiparasitic agents. The current method provides a highly favorable synthetic strategy for the efficient construction of important therapeutic agents containing polysubstituted aromatic core structures.…”

“…[1] Furthermore, b-enamino esters are employed as key starting reagents for the synthesis of substituted pyra-Quinones represent one of the most widely distributed structural classes in nature, [17] and compounds belonging to this class can be found in a large number of important pharmacophores [18] associated with anti-cancer, antibacterial, antimalarial, fungicidal, and antiparasitic agents. [1] Furthermore, b-enamino esters are employed as key starting reagents for the synthesis of substituted pyra-Quinones represent one of the most widely distributed structural classes in nature, [17] and compounds belonging to this class can be found in a large number of important pharmacophores [18] associated with anti-cancer, antibacterial, antimalarial, fungicidal, and antiparasitic agents.…”

“…Given the importance of N-substituted phthalimide derivatives in pharmacochemistry, [32] a wide range of N-substituted maleimides 1c-h was also investigated under the optimized reaction conditions, and gave the corresponding oxidative aromatization products 3, albeit in slightly lower yields in the range of 35-71% (Table 3, entries 4-13). In comparison, the use of N-alkyl-substituted maleimides resulted in lower yields because the formation of some other by-products that could not be separated and characterized as they were not sufficiently stable under acidic conditions (Table 3, entries [14][15][16][17][18][19]. Based on these results, we were able to establish that the reaction proceeded smoothly with N-aryl-substituted maleimides 1c-f and that electron-donating substituents on the benzene ring favored the formation of product 3.…”