Iron (?) Complexes For Reduction Of NAD~+ Analogues And Catalytic Hydroboration Of Pyridines

Dihydropyridines are prevalent in natural products,coenzyme NAD(P)H and its model compounds.The NAD~+/NADH models undergo dearomatization/aromatization of pyridine motifs and play viatal roles in reduction-oxidation metabolism and organocatalysis.Furthermore,dihydropyridines are often used as important intermediates in transformations that provide straightforward access to pharmacologically active molecules.Owing to their importance in biological systems and chemical synthesis,methods for preparation of dihydropyridines have been a central point in biomimetic chemistry over the past few decades.Transition-metal catalyzed reduction of NAD~+ models and dearomatization of pyridines based on precious metals such as Ru,Rh and Ir usually proceed under mild conditions with high chemo-and regioselectivity.However,works based on abundant metals are sparse,thus the mechanism is not well investigated.In this thesis,the Iron hydride of piano-stool type Cp*(P-P)FeH(Cp*= C5Mes,P-P = diphosphine ligands)were synthesized,and the hydride transfer from Fe-H to NAD~+ analogues were examined systematically.Based on the studies of the mechanism for the reduction of pyridinium cations,new Iron(?)complex[Cp*(P-S)FeNCMe]was synthesized.The regioselective 1,2-hydroboration of pyridines were achieved using[Cp*(P-S)FeNCMe]as catalyst through metal-ligand cooperation.The details were obtained as follows:1.Hydride transfer from Cp*(P-P)FeH to NAD~+ analogues were achieved.During the reduction,two pathways for hydride transfer,"single step H-" transfer to pyridinium and a "two step e-/H" transfer for acridinium cations were observed.(?)According to the kinetic studies,the BNA+ was first reduced at C6 position,affording 1,6-BNAH,which converts to thermally stable 1,4-BNAH slowly through isomerization.Combined with the substitute effects during the hydride transfer,the results suggested one step H" transfer to pyridium cations.In addition,the rate constant of H-transfer was sensitive to steric effects of the metal center.(?)In the reduction of 10-methylacridinium cation,the reaction was initiated by electron transfer to gave[Fe-H]+ and Acr·,followed by dimerization of Acr· to afford Acr2.When bulkier 9-phenyl-10-methylacridinium was used as accepter,two step e-/H were achieved.2.Solvent effects on the reduction of BNA+ with Cp*(Ph2PtBuPPh2)FeH were examined,which suggested that coordinating ligands such as MeCN not only act as ligand to stabilize[Cp*(Ph2PtBuPPh2)Fe]+ to form[Cp*(Ph2PtBuPPh2)Fe(NCMe)]+,but also' participates in the hydride transfer process.In the absence of MeCN,the reduction of BNA+ afford[Cp*(Ph2PtBuPPh2)FeN2]+ and BNAH in THF.When the reaction was conducted in CH2Cl2,the produced[Cp*(Ph2PtBuPPh2)FeN2]+ catalyzed the reaction of Fe-H with CH2Cl2 to afford Cp*(Ph2PtBuPPh2)FeCl2 and C2H4Cl2,which hampers the hydride transfer.3.New Iron complex[Cp*(P-S)FeNCMe](P-S = Ph2PC6H4S-)were synthesized and used as catalyst in the regioselective 1,2-hydroboration of pyridines through metal-ligand cooperation.The reaction was compatible with a broad of pyridines and functional groups.Mechanism studies suggested the ligand of P-S served as base to activate H-B bond,cooperating with the metal center to achieve the hydroboration of pyridine.The results are fundamental for understanding the hydride transfer from Iron hydride to NAD~+ analogues and metal-ligand cooperation in catalysis,which provide valuable insight for designing of catalysis for reduction of pyridines based on abundant metals.