Research Based On Asymmetrical Alkylation Of Cyclic Ethers

Nucleophilic addition to a prochiral,cyclic oxocarbenium ion provides a powerful and efficient strategy for the synthesis of a-substituted oxygen heterocycles,fundamental structural motifs in complex natural products and biologically active molecules.While various reliable methods for diastereoselective additions to oxocarbenium ions have been identified,only a few catalytic enantioselective variants are demonstrated.On the other hand,oxocarbenium ion formation canbe initiated via the selective oxidation of the C-H bond adjacent to an oxygen atom.The strategy is attractive because it provides excellent opportunities to straightforwardly access the target from readily accessible precursors with minimum intermediary refunctionalizations and high atom economy.In particular,the cross-dehydrogenative coupling(CDC)of two C-H bonds proved to be an elegant method for the purpose.The majority of such CDC reactions involve the functionalization of the a-C-H bond of nitrogen in amines,with few precedents regarding the coupling of C-H bond a to ethereal oxygen probably due to the higher oxidation potential of the latter.Given the importance of O-heterocyclic motifs within biologically relevant molecules,and the opportunity that asymmetric alkylation of aldehydes would afford heterocycles with multiple stereogenic centers,we herein document the first enantioselective and oxidative cross-coupling of Chromene with aldehydes.We also have developed an efficient copper(Ⅱ)-catalyzed oxidative cross-coupling reaction of cyclic benzylic ethers with a variety of simple carbonyl compounds employing the inexpensive reagent Na2S2O8 as the terminal oxidant.The low cost,negligible toxicity,and ease of handling of the oxidant combined with the absence of hazardous byproducts,are attractive.The method does not require any solvent,and the workup consists of simple filtration.To the best of our knowledge,this is the first example of the use of Na2S2O8/Cu(Ⅱ)to promote CDC reaction with ethers,leading to C-C bond formation.The development of other peroxydisulfate-mediated oxidative coupling reactions is currently under investigation and will be disclosed in due course.