Research On The Deoxygenative Reduction Of Aldehydes/Ketones For C-C Bonds Construction

Ketone compounds bearing unsaturated C=O bonds,are prevalent molecular skeletons in small molecule drugs,nature products.Construction of new C-C bonds through deoxygenative reduction of C=O bonds are of high importance in both academia and practical application.At present,the reductive deoxygenation of ketones has mainly achieved by using transition-metal-catalysis under harsh reaction conditions,which suffers from several disadvantages such as high synthetic cost,and tedious steps.Therefore,the development of efficient metal-free methods toward reductive deoxygenation of carbonyl compounds catering to C-C construction is highly desired.In this thesis,several metal-free transformation approaches have been developed based on the deoxygenation of aryl ketones/alicyclic ketones/aromatic aldehydes.The main content of this thesis falls within three components:1.Metal-free reductive deoxygenation ofα-H aryl ketones to corresponding alkenes.The optimal conditions were established with a combination of 1,1,3,3-tetramethyldisiloxane(TMDS),triflic acid,and tetrahydrofuran(THF)reaction at 35℃for 5 h,with the highest yield of alkene product up to 92%.The method avoids heavy metal residues,brings wide functional group compatibility and high reactivities.A multistep reaction pathway is proposed,in which aryl ketones are reduced to alcohols,followed by fast sequential dehydration/β-elimination process to give alkenes.2.Acid/siliane promotes reductive cross-coupling of ketone with indole to construct Csp~2-Csp~3 bonds.Triflic acids/silanes as cooperative reductants enable the straightforward access to C3-alkylated indole.The metal-free protocol features a broad substrate scope and cheap reductant.The late-stage functionalization of drug molecules was successful by using this strategy.3.Electrochemically enabled reductive arylation of aryl aldehydes/ketones with cyanobenzenes.The chemo-selectivity was controlled by the applied voltage and time for selective alkanes or alcohols product formation.This approach features a mild conditions,high energy efficiency,matching the concept of green chemistry.