Visible‐Light‐Mediated [4+2] Cycloaddition of Styrenes: Synthesis of Tetralin Derivatives

Abstract

We report a formal [4+2] cycloaddition reaction of styrenes under visible‐light catalysis. Two styrene molecules with different electronic or steric properties were found to react with each other in good yield and excellent chemo‐ and regioselectivity. This reaction provides direct access to polysubstituted tetralin scaffolds from readily available styrenes. Sophisticated tricyclic and tetracyclic tetralin analogues were prepared in high yield and up to 20/1 diasteroselectivity from cyclic substrates.

Nickel/NHC‐Catalyzed Asymmetric C−H Alkylation of Fluoroarenes with Alkenes: Synthesis of Enantioenriched Fluorotetralins

“…[5a] Furthermore,t he use of aN icatalyzed CÀHa lkenylation, originally reported by Nakao and co-workers,gave apolyfluorostyrene in high yield (8). [5d] Furthermore,aNi-promoted hydrodefluorination delivered ac hiral tetralin product (9). [27] Thus,t he combination of the current asymmetric CÀHa lkylation method with the hydrodefluorination process provides an efficient formal enantioselective hydroarylation of simple arenes,which is achallenging, yet important transformation.…”

“…[3] Among them, the C À Hfunctionalization of readily available fluoroarenes is the most atom-and step-economical method. [8] Ty pically,t etralin systems are synthesized through Friedel-Crafts type cyclization of aryl derivatives [9] or hydrogenation of naphthalene derivatives. Importantly,a ne nantioselective CÀHa ctivating cyclization of polyfluoroarenes to access optically active fluorotetralin skeletons has not been reported, though these fluorotetralins serve as important bioisosteres of both tetralin and heterocycle scaffolds for drug design, [7] and are commonly found in pharmaceuticals and materials (Figure 1).…”

“…[4,5] Despite recent progress in racemic reactions, [5] the direct catalytic asymmetric CÀHf unctionalization [6] of polyfluoroarenes remains unknown. [8] Ty pically,t etralin systems are synthesized through Friedel-Crafts type cyclization of aryl derivatives [9] or hydrogenation of naphthalene derivatives. [8] Ty pically,t etralin systems are synthesized through Friedel-Crafts type cyclization of aryl derivatives [9] or hydrogenation of naphthalene derivatives.…”

“…Importantly,a ne nantioselective CÀHa ctivating cyclization of polyfluoroarenes to access optically active fluorotetralin skeletons has not been reported, though these fluorotetralins serve as important bioisosteres of both tetralin and heterocycle scaffolds for drug design, [7] and are commonly found in pharmaceuticals and materials ( Figure 1). [8] Ty pically,t etralin systems are synthesized through Friedel-Crafts type cyclization of aryl derivatives [9] or hydrogenation of naphthalene derivatives. [10] However,t hese two methods are not applicable to chiral fluorotetralin synthesis due to the challenges associated with chemo-, regio-, and stereocontrol and the facile hydrodefluorination side reaction [11] (Scheme 1A,B).…”

Oxidative [4+2] annulation of styrenes with alkynes under external-oxidant-free conditions

“…Recently, the alkene radical cation species has been increasingly utilized as key intermediate in the organic synthesis 18 – 20 . The radical cation D–A reaction has already emerged as a useful synthetic method, which can be carried out under milder conditions with high regioselectivity and reactivity than the analogous thermal [4 + 2] cycloaddition involving neutral or electron-rich dienophiles 21 – 24 . The photoredox catalysis provides a convenient tool to access such highly reactive odd-electron species under mild conditions 25 – 36 .…”