Alkyl-spirocyclization And Dehydrogenation Coupling Initiated By Oxidative Decarbonylation Of Aliphatic Aldehydes

Spirocyclohexadienone is one of the important structural units in natural products,biologically active molecules and drug molecules;and the radical bifunctionalization and ipso-cyclization of N-arylcinnamamide or N-arylpropynamide that is a simple and efficient way to introduce various functional groups into spirocyclohexadienone.On the other hand,peptide drugs are widely used in clinical treatment,such as the treatment of diabetes,AIDS,rheumatoid and tumor viruses,and modified peptides can significantly improve their biochemical activity and pharmacokinetics.Therefore,the development of novel and efficient methods to realize the direct functionalization ofα-amino acid derivatives C(sp~3)-H has received extensive attention.Therefore,in this disertation,cheap and easily available aliphatic aldehydes are used as alkylation reagents,and alkyl radicals are generated through decarbonylation initiated by radicals,which realizes the decarbonylation of alkyl-spirocyclization with N-arylcinnamamide,and the glycine derivative C(sp~3)-H dehydrogenation coupling.1.We have developed an efficient Fe-catalyzed oxidative decarbonylation of aliphatic aldehydes with the alkyl-spirocyclization of N-arylcinnamamide.This method uses DTBP as a radical initiator and oxidant to oxidative decarbonylation of aliphatic aldehydes to form 1~o,2~o and 3~oalkyl radicals,through radical addition,intramolecular ipso-cyclization,dearomatization,and constructed two C(sp~3)-C(sp~3)and one C=O bond,a series of alkyl substituted spirocyclohexadienones were synthesized.2.We have developed a convenient Fe-catalyzed oxidative decarbonylative C(sp~3)-H dehydrogenation coupling reaction of glycine derivative and aliphatic aldehyde.DTBP as oxidant and radical initiator,readily available aliphatic aldehydes were decarbonylated into alkyl radicals.Then,glycine derivatives are oxidized into imine compounds;finally,a series of unnatural amino acids substituted with different alkyl are synthesized by radical addition.The method have a simple experimental operation and broad substrate tolerance,it was applied to various glycinate,amide,dipeptide and so on.