Regioselective Synthesis of Bicyclic and Polycyclic Systems by Cycloaddition Reactions of Alkenyl p-Benzoquinones

Abstract

An efficient [3 + 2]/[4 + 2] or double [4 + 2] cycloaddition strategy has been established for the synthesis of heterocyclic systems under mild conditions. The reaction pathway is governed by the nature of reaction partner. Several dihydrofurocoumarin, furopyranocoumarin, dihydrofuran, dihydrobenzopyran, and dihydrobenzofuran derivatives were obtained as single diastereomers from cyclic or acyclic enol ethers and styrenes. This one-pot transformation constructed C-C and C-O bonds and generated molecular complexity by domino/tandem process to produce the heterocyclic systems in good yields. The ring closure of domino protocol was highly stereoselective and resulted in the formation of cis-fused systems.

Donor‐Acceptor Cyclopropanes in the Synthesis of Carbocycles

“…[27] However, furan derivatives can also react as 2p-components affording products of (2 + 1)-, [3,28] (2 + 2)-, [29] (2 + 3)- [30] and (2 + 4)-cycloadditions. [31] Therefore, we have studied the reactions of some furan derivatives with the aim to determine their reactivity against D-A cyclopropanes 1. Furan and 2-methylfuran failed to give any cycloadduct under all studied conditions yielding only tar.…”

Organocatalytic C(sp3)–H Functionalization of 5-Methyl-2,3-dihydrofuran Derivatives with Trifluoropyruvates via a Sequential exo-Tautomerization/Carbonyl-Ene Process

“…The great challenges might come from the weak acidity and weak nucleophilicity of the methyl group at the C6 position, which resulted from the thermodynamically stable and electron-rich enol ether moiety of dihydrofuran. Moreover, a competitive direct carbonyl-ene reaction at the C4 position is kinetically favored than exo -tautomerization due to the high reactivity of the enol ether to participate in cycloaddition and nucleophilic addition . As a continuation of our research interest in the development of an organocatalytic C­(sp 3 )–H functionalization strategy for the one-step assembly of pharmaceutically important targets, , herein, we reported an organocatalytic C­(sp 3 )–H functionalization of 5-methyl-2,3-dihydrofuran derivatives with trifluoropyruvates to synthesize potentially bioactive CF 3 -substituted 2,3-dihydrofurans in excellent yields.…”

“…Substituted 2,3-dihydrofurans are ubiquitous in natural products and medicinal molecules, such as aflatoxin B 1 , clerodin, austocystin A, and citridone A (Figure ). They have also been used as synthetic intermediates in the construction of highly functionalized tetrahydrofurans . Meanwhile, the trifluoromethyl group (CF 3 ) represents a privileged pharmacophore in numerous pharmaceuticals with remarkable bioactivities, such as Efavirenz (HIV-RT inhibitor), (+)- erythro -Mefloquine (antimalarial), and ZK-216348 (selective glucocorticoid receptor agonist) (Figure ).…”

[3 + 2] Coupling of Quinone Monoacetals with Vinyl Ethers Effected by Tetrabutylammonium Triflate: Regiocontrolled Synthesis of 2-Oxygenated Dihydrobenzofurans

“…Attracted by the importance of this skeleton, various groups have reported the construction methods of it by several approaches. − However, many cases require the stepwise approach from readily available starting materials. − In contrast, the coupling of phenols with vinyl ethers can simultaneously form C–C and C–O bonds in one step . Especially, the recent advancement of palladium-catalyzed reactions and concomitant ligand chemistry enabled the stereoselective synthesis of 2-oxygenated dihydrobenzofurans (Scheme a). , These methods require ortho -halogenated phenols as the starting materials and specific expensive ligands.…”

“…However, this method produced the products only in low to moderate yields . As remarkable alternatives to phenols, 1,4-benzoquinones were evaluated by several researchers . Notably, Corey studied the [3 + 2] coupling of some benzoquinone derivatives with 2,3-dihydrofuran and utilized this approach for the stereoselective total synthesis of aflatoxin B 2 (Scheme c) .…”