Photocatalyzed Giese Reaction And Cyclopropanation Of Vinylphosphonates

a-Aryl phosphonates have received considerable attention due to their interesting biological properties.Despite their importance,the methods to synthesize them are limited,and often have risctricted substrate scopes.In this thesis,the recent renaissance of the Giese reaction aided by the thriving visible-light photocatalysis was briefly discussed,and the utilization of vinylphosphonates as the radical trap in the photocatalized redox-neutral Giese reaction,together with the cyclopropanation of vinylphosphonates via radical methylene migration was introduced.This dissertation is mainly composed of the following two parts:The first part briefly discusses the photo-redox decarboxylative process and the olefin substrates in Giese type reactions that have come along within the past few years,putting forward the light induced decarboxylative addition of vinylphosphonates.The reaction condition was screened using diethyl a-phenyl ethenylphosphonate and benzyloxyacetic acid as the model substrate.After the ethenylphosphonate was stirred under r.t.for 12 to 24 h with the radiation of a 9 W blue LED with carboxylative acid(2.5 equiv),the photocatalyst Ir[dF(CF3)ppy]2(dtbbpy)PF6(1 mol%),the base Cs2CO3(1.5 equiv),and DMSO as the solvent(0.02 M),the yield reached 92%.The scope of the carboxylic acid was investigated,and it was revealed that carboxylic acids with electron donating groups performed well in this protocol,while those with electron withdrawing groups failed to deliver any product.The investigation of the scope of the phosphonate showed that except the benzofuran substituted substrate,common a-aryl ethenylphosphonates performed well in this reaction.Various functional groups were well tolerated in this protocol,and will leave halogen substitutes on the phenyl group untouched,providing the opportunity for further functional group interchanges.This protocol can also be used to introduce acetal groups,when dimethoxyl acetic acid was used as the formyl group equivalent,the acetal product can undergo a subsequent hydrolysis to release the aldehyde,which can be transformed to fosmidomysin analogue intermidiates after reductive amination and acylation.The second part briefly discusses the cyclopropanation of olefins via radical methylene migration,the nature and the recent applications of hypervalent silicates were also described.The addition-cyclization of vinylphosphonates by chloromethyl silicate induced by photoredox catalysis was put forward.Screening the reaction condition with diethyl a-phenyl ethenylphosphonate as the model substrate revealed that when the ethenylphosphonate and potassium[18-Crown-6]bis(catecholato)-chloromethylsilicate(2 equiv),and the catalyst Ir[dF(CF3)ppy]2(dtbbpy)PF6(2 mol%),were dissolved in DMSO(0.033 M)and admitted to radiation with a 9 W blue LED for more than 12 h,the yield reached 91%.The scope of a-aryl ethenylphosphonates demonstrated that electron donating groups attached to the phenyl ring will enhance the reaction,obtaining the product in good to excellent yields,while electron withdrawing groups on the aryl group will hinder the formation of cyclization products,and yield instead the mixture of the cyclopropanation and the addition product.a-Alkyl ethenylphosphonate can also undergo this reaction,only with longer reaction timer and the yield will be lower.The hyper-valent silicate used in this protocol is easy to synthesize and handle,and provides a rare approach to a-halo-substituted alkyl radicals.The scope of this protocol is fairly wide and various functional groups including halogen substitutes on the phenyl group are well reserved,leaving the possiblilities of further transformations open.This protocol can also be used to synthesize more exquisite molecules like estrone derivatives,making it a possible choice in the synthesis of complex natural products.