Nickel-Catalyzed Reductive Cross-Coupling Of Trifluoroethyl Halides And Related Derivatives With(Hetero) Aryl Halides/Synthesis Of Polyethylene Glycol Macrocyclic Sulfate

The volume,acidity,lipophilicity,chemical and metabolic stability of organic molecules could be changed by the introduction of trifluoromethyl groups,thus trifluoromethyl groups have wide and successful applications in pharmaceutical chemistry.Much attentions have been paid to synthesize such molecules by novel and effective methods in recent years.However,they are not easy task.By nickel-catalyzed reductive cross-coupling reactions,we had developed two efficient methodologies to synthesize arenes derivatives whose benzyl position were substituted by trifluoromethyl group.Polyethylene glycol and related derivatives were widely used for drug modifications or biomedical imaging agents,but they were difficult to synthesize.By the effective synthesis of polyethylene glycol macrocyclic sulfate,we had laid a good foundation for the synthesis of monodisperse polyethylene glycol and its derivatives with high molecular weight.The full paper consists of three parts.I,Nickel-Catalyzed Reductive Cross-Coupling Reactions of(Hetero)Aryl Iodides(Bromides)with Fluorinated Secondary Alkyl BromidesIn this part,we had developed an effective method that could introduce CF3 or CF2COiEt substituted secondary alkyl groups into(hetero)arenes benzyl position under mild reaction conditions.The reactions feature with wide substrates scope and excellent functional groups tolerance.FeBr2 acted as additive is the key point to improve yields,reduce reaction temperature and suppress side reactions.The preliminary mechanism studies showed that this reactions involved single electron transfer pathway.This is also the first publication of reductive cross-coupling reaction in organofluorine chemistry field.?,Nickel-Catalyzed Reductive Cross-Coupling Reactions of(Hetero)Aryl Bromides(Chlorides)with 2-Chloro-1,1,1-trifluoroethaneIn this part,we realized the coupling of cheap and easy available industry chemical material 2-chloro-1,1,1-trifluo,ro.ethane with(hetero)aryl bromides(chlorides).It can successfully introduce 2,2,2-.trifluoroethyl group into(hetero)arenes under mild and cheap conditions.This methodology behaves wide substrates scope and excellent functional groups tolerance,and suits for fluorination modification of multiple drugs.The preliminary mechanism studies showed that this reactions also involved single electron transfer pathway.? The Synthesis of Polyethylene Glycol Macrocyclic SulfateIn this part,by employ kinds of polyethylene glycol with short chain length,we synthesized various cyc lic size of polyethylene glycol macrocyclic sulfate.They can be used for the synthesis of momodisperse polyethylene glycol and related derivatives with high molecular weight.Compared with other methods,our novel mean features with short synthetic procedure,high efficiency,and easy purification.