Study On The Construction Of Quaternary Carbon Centers By Tertiary Alkyl Electrophiles And The Formation Of C-B Bond

All-carbon quaternary stereocenters widely exist in biologically active natural products and pharmaceutical compounds.The conventional methods involve transition metal-catalyzed coupling of tertiary alkyl-metallic nucleophiles such as Grignard reagents with different electrophiles.However,these methods generally suffer from narrow substrate scope,poor functional group compatibility,and/or low reactivity and efficiency.Therefore,the development of a mild,more versatile method for the synthesis of quaternary carbon compounds is highly demanded in the pharmaceutical industry.On the other hand,photocatalytic organic synthesis is a difficult but hot topic in organic synthesis.The present photochemistry generally requires the use of a photocatalyst,which generally arises from expensive transition metals.Therefore,development of a photo-induced method to generate a tertiary radical for C-B bond formation that does not require a photocatalyst is of interest.Based on this background,this thesis consists of the following three sections:1.Our previous work showed that nickel-catalyzed reductive coupling strategy can be effectively used for the coupling of primary and secondary alkyl halides with other electrophiles,so as to form different C-C bonds.On this basis,we developed a method enabling the alkenylation of the very challenging cyclotryptamine-derived tertiary alkyl halides to generate alkenylated quaternary carbon centers.The reaction employed 10 mol%of NiI2 has the catalyst,100 mol%of MgCl2 and LiCl as the additives,100 mol%of 3-fluoropyridine as the ligand and DMSO as solvent.The reaction displayed excellent substrate compatibility,and the yields could reach above 70%;2.On the basis of the first part,we achieved the coupling reaction of cyclotryptamine-derived tertiary alkyl halides with aryl halides under similar reaction conditions.The reaction employed 10 mol%of Ni(acac)2 as the catalyst,100 mol%of MgCl2,300 mol%of LiCl as the additives,100 mol%of 3-fluoropyridine as the ligand and DMF as solvent.The method was successfully extended to the synthesis the key intermediate of natural compound(+)-Asperazine;3.Design and synthesis of a new method for the construction of C-B bonds by cleavage of readily available C-O bond under visible photo-induced conditions has been achieved.Specifically,we used tertiary alkyl oxalates as the C-O bond sources which are easily prepared from the alcohols.By light irradiation in the presence of diboron(B2Cat2),we were able to obtain tertiary alkyl-Bpin products after conversion of the alkyl-BCat with pinacol.The method did not require any photocatalyst.