A practical and modular three-component alkene oxyarylation with benzoquinone and H 2 O to rapidly access C 3substituted dihydrobenzofurans has been developed. The (NH 4 ) 2 S 2 O 8 -mediated redox-relay process has an excellent regioselectivity and functional group tolerance and exhibits a broad scope of simple alkenes, rapidly furnishing a variety of the substructures that would require multiple steps to prepare with traditional methods. Mechanistic studies revealed a dual role of benzoquinone serving as both the arylation agent and the origin of dihydroquinone for the reductive cyclization step.C 3 -Substituted dihydrobenzofurans (DHBs) are key motifs in a number of bioactive natural molecules and have been used for many pharmaceutical applications (Figure 1a). 1 The most frequently employed approach to access such motifs relies on intramolecular arylation of an allylic ether of o-halophenol either through organotin-mediated radical cyclization or through transition-metal-catalyzed Heck-type cyclization, both of which require multiple steps for substrate prefunctionalization (Figure 1b). 2,3 On the other hand, acid-catalyzed [3 + 2] cycloaddition of alkenes with benzoquinone (BQ) represents one of the most practical methods for rapid DHB skeleton construction (Figure 1c). 4 Due to the innate alkene polarization, the biomimetic oxyarylation process follows Markovnikov's rule, predominantly giving C 2 -substituted DHBs with oxygen bonding to the more substituted olefinic carbon. 5,6 Moreover, the reaction mechanism requires electron-rich alkenes such as styrenes and enol ethers, with the widely existing simple olefins intact. Accordingly, direct access to C 3 -substituted DHBs by reversing the alkene polarization in oxyarylation with BQ would be an attractive, but challenging, project to pursue. 7 Recently, we have disclosed an (NH 4 ) 2 S 2 O 8 -mediated threecomponent oxyalkynylation of alkenes using H 2 O as an oxygenation agent. 8 Notably, the method exhibited reversed regioselectivity to the existing three-component carbooxygenation of alkenes. Mechanistic studies revealed that the reversed regioselectivity was dictated by an alkene radical cation species that underwent hydration to give anti-Markovnikov β-oxyl radical 1 for the subsequent alkynylation process. Given the electron-deficient property of BQ toward radical addition, 9 a two-step redox-relay approach for C 3substituted DHBs was initially designed: (1) alkene 2 proceeds through regioselective hydroxylation to generate an anti-Markovnikov β-oxyl radical 1 that participates in oxidative C−H alkylation of BQ to yield quinone 3, and (2) 3 undergoes reductive cyclization to furnish the expected C 3 -substituted DHB 4 (Figure 1d). Herein, we report an (NH 4 ) 2 S 2 O 8mediated metal-free three-component oxyarylation of alkenes
A one-pot deracemization of β,γ-alkynyl α-amino esters consisting of an aerobic oxidation and chiral phosphoric acid-catalyzed asymmetric transfer hydrogenation has been described.
An efficient oxidative C-H alkynylation of N-carbamoyl tetrahydroisoquinolines mediated by a TEMPO oxoammonium salt has been established. A variety of electronically varied N-carbamoyl tetrahydroisoquinolines reacted with a range of alkynyl potassium trifluoroborates smoothly under mild metal-free conditions. Dihydroisoquinolines were also suitable components for the reaction. The synthetic applicability of the method for facile access to structurally diverse bioactive molecules was further demonstrated.
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