Palladium-Catalyzed Cross-Coupling Of Unactivated Alkylzinc Reagents With 2-Bromo-3,3,3-Trifluoropropene And And Its Application In The Synthesis Of Fluorinated Amino Acids

Fluorinated amino acids are important amino acids.Among them,amino acids containing trifluoromethyl?CF₃?and difluoromethyl?CF₂H?have attracted extensive attention in polypeptides and proteins.Therefore,the efficient synthesis of this type of amino acids has attracted wide interest of chemists and made rapid progress.However,efficient and practical methods to access such valuable fluorinated amino acids are limited.Based on the theory and research,we designed a new synthesis methodology that palladium-catalyzed cross-coupling of unactivated alkylzinc reagent with 2-bromo-3,3,3-trifluoropropylene?BTP?.And the system was also suitable for benzylzinc reagent.Then,we applied it to the synthesis of fluorinated amino acids,and synthesized eight amino acids containing trifluoromethyl,difluoromethyl and difluoroalkyl.The full text is divided into the following two chapters.Chapter ?:Palladium-Catalyzed Cross-Coupling of Alkyl and Benzylzinc Reagents with 2-Bromo-3,3,3-TrifluoropropylenePart ?:Palladium-Catalyzed Cross-Coupling of Unactivated Alkylzinc Reagents with2-Bromo-3,3,3-Trifluoropropene.In this section,2-bromo-3,3,3-trifluoropropylene,alkylzinc reagent as raw materials,tetrahydrofuran as solvent,Cphos-Pd-G3 as catalyst,and reacted for 8 hours at 90 ^oC.The palladium-catalyzed cross-coupling reaction of alkylzinc reagent with 2-bromo-3,3,3-trifluoropropylene was realized.The reaction conditions are mild,the substrates are suitable for a wide range of applications,and the functional groups are compatible well.The use of Cphos-Pd-G3 is the key to increase yield and inhibit side effects.Finally,15compounds were synthesized.Part ?:Palladium-catalyzed cross-coupling reaction of benzylzinc reagent with2-bromo-3,3,3-trifluoropropyleneIn this section,2-bromo-3,3,3-trifluoropropylene,benzylzinc reagent as raw materials,tetrahydrofuran as solvent,Pd?TFA?₂ as catalyst,S-phos as ligand,and reacted for 8 hours at 90 ^oC.The palladium-catalyzed cross-coupling reaction of alkylzinc reagent with 2-bromo-3,3,3-trifluoropropylene was realized.The reaction conditions are mild,the substrates are suitable for a wide range of applications,and the functional groups are compatible well.The use of S-phos is the key to increase yield and inhibit side effects.11compounds were synthesized.Chapter ?:Derivative Modification of Amino AcidsIn this chapter,we use the fluorinated amino acids as raw materials to derive a series of fluorinated amino acid derivatives.Eight compounds were synthesized.