Studies On Visible-light-induced C(sp~3)-H Functionalization Of Glycine Derivativess

Unnaturalα-amino acids are widely found in active natural products and pharmaceutical molecules,and are widely used as important synthetic building blocks in organic synthesis and pharmaceutical synthesis.Glycine is the simplestα-amino acid,and the directα-C(sp~3)-H functionalization of glycine derivatives has proved to be a powerful tool for the rapid and atomic economic synthesis of unnaturalα-substituedα-amino acids.Over the past decade,visible-light photoredox catalysis has emerged as a powerful tool in organic synthesis.However,the examples on photocatalyticα-C(sp~3)-H functionalization of glycine derivatives are still limited,and the reported reactions usually require the use of expensive transition metal photosensitizers such as Ru and Ir complexes.The research work of this thesis is focused on visible light-induced direct C(sp~3)-H functionalization of glycine derivatives via cerium catalysis or auto catalysis.Accordingly,the main research content of this paper includes the following three parts:1)A visible light-induced,thiols catalytic oxidative dehydrogenative coupling reaction of glycine derivatives with thiols has been accomplished.This reaction provides a simple method for the generation ofα-thioglycine derivatives(40 examples,33%-95%yield)under mild conditions(room temperature,air atmosphere,visible light irradiation).The process is noteworthy in that it does not require photosensitizer or additional oxidant.It has been shown that the disulfide formed by the autooxidation of thiol is the photosensitive species in this reaction.This reaction not only provides a new method for the synthesis ofα-thioglycine derivatives,but also opens a new avenue for the C(sp~3)-H functionalization of glycine derivatives.2)A Ce(Ⅲ)catalyzed visible light-induced aerobic oxidative dehydrogenative coupling reaction between glycine derivatives and arylamine derivatives has been developed.This reaction could achieve the concise synthesis of a series of arylglycine derivatives(27 examples,40%-90%yield)under mild conditions.The process is noteworthy in that it does not require a photoredox catalyst or an additional oxidant.It has been shown that the complex formed between glycine derivatives and Ce(Ⅲ)salts is the photosensitive species in this reaction.This method not only provides a new method for the C(sp~3)-H functionalization of glycine derivatives,but also represents a new entry for the cerium photocatalysis.3)By using the visible light-induced oxidative cross-coupling reaction between glycine esters and indoles(developed by our group)as a key step,the pivotal skeleton of Echinosulfonic Acid natural products—3,3’-bisindolylmethane was synthesized from commercially available p-aminoanisole and methyl bromoacetate.The natural product Echinosulfonic Acid D was synthesized by three steps with a total yield of 7%.The key skeleton intermediate of Echinosulfonic Acid C was also synthesized.