Synthesis Of Ketones And Esters Via Functionalization Of Inert C-H Bonds Based On Radical Mechanisms

Ketones and esters are widely found in nature.In addition,they are also highly valuable in the fields of pharmaceuticals and fine chemicals.On the other hand,inert C-H bond functionalizations via radical pathways are recently emerging as promising and reliable strategies for modern organic synthesis due to their inherent advantages such as no need for pre-activation of substrates,reduced waste production and high atom-economy.Under the above mentioned background,several radical-based C-H bond functionalization reactions have been designed and studied in this thesis.From these reactions,novel methods for the synthesis of?-alkyl ketones,2-aminobenzophenones and esters were successfully established.The contents of this thesis are included in the following five Parts:In Part I,recent studies on the develoment of new methods for the preparation of?-alkyl ketones,2-aminobenzophenones and esters are briefly reviewed.In Part II,a microwave-promoted?-alkylation of ketones with cycloalkanes as the alkylating reagents is developed.Mechanistically,the alkylation should involve the cross-dehydrogenative coupling of C?sp³?–H bonds of ketones derivative with those of cycloalkanes via a radical pathway under metal-free conditions.This accomplishement is remarkable as selective cross-coupling of different carbon radicals is a great challenge because of their inherent instability and diverse reactivity.With advantages such as inexpensive and abundant substrates,metal-free conditions,and excellent sustainability with hydrogen gas as the only byproduct,this protocol is expected to find wide applications in related areas.In Part III,an efficient and regioselective synthesis of N-nitroso-2-aminobenzophenones through the one-pot three-component cascade reactions of anilines with tert-butyl nitrite and?-oxocarboxylic acids?as the acylation reagents?under the catalysis of Pd?OAc?₂ is established.In addtion,direct treatment of the resulting mixture from the above mentioned acylation reactions with Fe/NH₄Cl led to a highly practical and all-in-one-pot preparation of 2-aminobenzophenones via the removal of the NO unit that is left behind in the in situ generated N-nitroso-2-aminobenzophenones without isolation and purification of any involved intermediates.Notably,this is the first example in which N-nitroso-2-aminobenzophenones were synthesized directly from anilines and?-oxocarboxylic acids in a highly regioselective manner by using tert-butyl nitrite as both a nitrosation reagent and an oxidant.Compared with literature methods,this novel protocol has notable features such as simple starting materials,mild reaction conditions,high efficiency and excellent regioselectivity.In Part IV,an efficient and novel method for the preparation of esters is developed via an oxidative esterification of aldehydes with alkyl halides in aqueous media.It is worth to be noted this esterification protocol is suitable for various kinds of aldehyde and alkyl halide substrates to give ester products with highly broad structural diversity.In addition,by using this method,an efficient and novel synthetic approach toward isobenzofuran-1?3H?-one was also successfully realized.Notable features of this method include direct use of commercially available and economical starting materials,wide substrate scope,good tolerance of various functional groups,sustainable oxidant,and no need of inert atmosphere or dry solvents.In part V,an alternative method for the synthesis of N-nitroso-2-aminobenzophenones from the reaction anilines with tert-butyl nitrite and benzaldehydes?as the acylating reagents?is studied.Preliminary results showed that in the presence of Pd?II?,aniline could react with tert-butyl nitrite and benzaldehyde smoothly to give N-nitroso-2-aminobenzophenones in a regioselective manner.By using aldehydes as the acylating reagents,this approach has higher atom economy.Further optimization studies of this reaction is currently underway.