One-Pot Synthesis of α-Carbonyl Bicyclic Furans via a Sequential Diels–Alder/5-Exo-Dig Cyclization/Oxidation Reaction

Abstract

A new one-pot approach to construct α-carbonyl bicyclic furans from easily accessible diynones is described. This reaction sequence proceeds via a Diels-Alder cycloaddition reaction catalyzed by dimethylaluminum chloride followed by a 5-exo-dig cyclization/oxidation reaction catalyzed by copper(II) chloride. This methodology generates α-carbonyl-functionalized dihydroisobenzofuran derivatives in good to excellent yields.

Synthesis of Dihydroisobenzofuran Carboxaldehyde Derivatives by a Silver‐Catalyzed Sequential Protodesilylation/Cyclization/Oxidation Reaction

“…This includes reducing waste, cost, and time, to name a few. Our group previously reported an efficient copper‐catalyzed cyclization/oxidation reaction of skipped diene intermediates to rapidly generate dihydroisobenzofuran ketone derivatives (Scheme a) . Herein, we demonstrate that silver catalysts can invoke a protodesilylation reaction followed by sequential cyclization/oxidation steps to provide dihydroisobenzofuran aldehydes (Scheme b).…”

“…Starting materials 2 were prepared as previously reported . Phenyl‐substituted enynones were well tolerated in this reaction to give products 3a – 3c in good yields (Table ).…”

“…Currently, the construction of dihydroisobenzofuranones, such as the total synthesis polyketide 1 , involves numerous synthetic steps . Only a limited number of synthetic methods have been reported for the generation of α‐carbonyl furan derivatives and reports on the synthesis of α‐carbonyl bicyclic furans, such as isobenzofurans, are scarce . Therefore, the development of efficient methods to quickly and efficiently arrive at this core structure would be beneficial for accessing this important class of biologically relevant molecules.…”

Divergence in Ynone Reactivity: Atypical Cyclization by 3,4‐Difunctionalization versus Rare Bis(cyclization)

“…To determine the feasibility of using ynonesasp recursors, 1-[2-(methylthio)phenyl]-3-phenylprop-2-yn-1-one( 2a) [2a] was treated with 2-(2-fluoropyridinium-1-yl)-1,1-bis[(trifluoromethyl)sulfonyl]ethan-1-ide (1)i na cetonitrile at room temperature. Interestingly, the formation of bis(triflyl)thioflavone (3a)w as observed (Scheme 2) rather than Friedel-Crafts-type bis(triflyl)alkylation or cyclobutenec onstruction( Scheme 1).…”

“…Ynones, versatile acetylenic platformst hat are readily available from the reaction of acyl chlorides and metal acetylides, have great potential for synthetic applications in nucleophilic additions, cycloadditions, and condensationr eactions. [1,2] However,t od ate, less conventional reactivities are underexplored. The presence of fluoroorganic moieties in organic compounds notably influences the physicochemical [3] and pharmacological properties of the fluorinated derivatives.…”