Synthesis And Application Of Organic-inorganic Hybrid Iron Catalysts

High optically active compounds are widely used in biopharmaceuticals,perfumes,pesticides and other fields.Asymmetric hydrogenation is one of the most effective methods for synthesizing highly optically active compounds.Chiral catalysts play an important role in asymmetric hydrogenation reactions.Noble metal(ruthenium,iridium,rhodium,palladium,etc.)catalysts are widely used in asymmetric hydrogenation.However,its application has been limited because of high toxicity and expensive price and low reserves.Therefore,it's important to replace noble metals with cheap metal as catalytic center and realize high activity and high selectivity asymmetric hydrogenation.In recent years,3d metal(manganese,iron,cobalt,etc.)catalysts have developed rapidly.Many cheap metal catalysts have been used in asymmetric hydrogenation of unsaturated double bonds.However,the activity of most cheap metal catalysts is much lower than that of precious metal catalysts.Besides,the stereoselectivity of products catalyzed by cheap metal catalysts is also low.This may be due to the difference in electronic structure between 3d metals and noble metals.The outer electronic structure of 3d metals(such as iron and cobalt)is 3d⁶4s¹ or 3d⁶4s².And the+1-valence electron binding energy of iron is 16.4 e V,however the+1-valence electron binding energy of ruthenium is 28.6 e V.Therefore,compared with noble metals,it has higher negative charge tolerance,and 3d metals have low affinity for electrons,which leads to the inactivation of reaction intermediates in the catalytic process.Therefore,there must be a new mechanism to compensate for the disadvantages of the structure of cheap metals to achieve the similar catalytic performance of noble metals.In addition,iron catalyst which using precious metal ligands can not achieve high enantioselectivity.Therefore,the development of chiral ligands that match iron is still an urgent problem to be solved.In this paper,we studied the electronic structure of cheap metal using iron catalysts.Combination of theoretical calculations and experimental methods,we discovered a new principle of activating 3d cheap metals:organic-inorganic hybridization.On the basis of this activation mechanism,chiral ligands for iron catalyst were designed to obtain high activity and high selectivity.Therefore,a synthesis method of chiral hybrid bisphosphine ligands was invented.The main research contents are as follows:(1)Study on the mechanism of organic-inorganic hybrid activation of iron catalystA series of P-N-N-P iron complexes(1-4)were synthesized,characterized,and tested for their catalytic activities to explore the structure-performance relationship of the catalyst precursors and intermediates.While the amino(imno)carbonyl complex(1)was highly active,the bis(amino)(2)and pyridyl-amino(3)analogues were inactive.Stoichiometric reactions were studied to elucidate the mechanistic causes of the success and failure of these iron catalysts.Although 1a and 1b are active and stable at room temperature,2a was found to be highly unstable under the catalytic conditions.Dearomatized pyridyl iron complexes(3b)were also inactive because they were too basic to be stable in the reaction solution.We refer to the crystal structures of 1c and 4a in reported literature,screen and establish the B3LYP/LANL2DZ calculation method.And we studied the electronic structures of 1a,1b,1c and 2a by a combination of spectroscopic and computational methods.The LUMO of 1a is a predominantly iron-centered nonbonding d orbital(54.5%iron).The doubly occupied HOMO-1 of 1a possesses 25.9%amido N atom character and 20.5%metal d character.This indicates that the monoanionic N atom undergoes some degree of?donation into the metal d orbital(ligand-to-metal?-donation).The same orbital also possesses 7.5%ene(amido)?*character,indicating the presence of a?-backdonation interaction with the ene(amido)group.Similarly,the LUMO of 2a is predominantly iron-centered(42.4%iron character).As seen in HOMO-1 of 2a,the bis(amido)dianion transfers electron density to the central iron ion via ligand-to metal?donation,giving a high electron density on the iron center.This is consistent with the vibrational frequency analysis by Fourier transform infrared(FTIR)spectroscopy which established that the iron center in 2a was more electron rich than that in 1a(?co=1880 vs 1901 cm^-1).Theoretical calculations on 1b revealed substantial?-backdonation to both the ene(amido)group and the carbonyl ligand,with 23.3%,9.6%and 6.2%of iron d,ene(amido)and carbonyl moieties in the HOMO-3 orbital,respectively.A large chemical shift(0.11 mm/s)was observed in the ⁵⁷Fe M?ssbauer spectrum of 1c due to the electron withdrawing effect of chlorine atom.And the small chemical shifts(-0.06 mm/s,-0.015 mm/s)were observed in the ⁵⁷Fe M?ssbauer spectrum of 1a and4b due to the higher charge density around the iron.The Fe 2p_3/2binding energies of 1a,1b,1c and4a(708.4 e V,707.7 e V,708.2 e V and 707.8 e V)further prove that the transfer of part of the charge is not the entire electron transfer at the iron metal center.Based on the above research conclusions,we propose a new mechanism for the activation of iron metal centers by organic-inorganic hybridization.(2)Synthesis and application of PNNP type iron catalyst containing substituentsTo further verify the correctness of the above mechanism,we synthesized four amine(imine)diphosphine iron precatalyst complexes with substituents at?and?positions relative to imino groups(5-7)or with enlarged chelate ring sizes(5,5,6-membered rings)(8).The introduction of methyl group in 5 and 6 reduced the catalytic activity but led to undiminished enantioselectivity as reaction proceed.Catalyst 7 is inactive for the transfer hydrogenation of acetophenone.The activity of the catalyst 8 is very high,and its conversion frequency can reach 85 s^-1 at 10 seconds,but the catalytic product is not selective.Catalyst 5 shows high activity for brominated and chlorinated acetophenone.For example,the yield of meta-chloroacetophenone in 10 minutes can reach 96%,and the yield of meta-bromoacetophenone in 5 minutes can reach 97%.To study the relationship between catalyst structure and catalytic performance,stoichiometric reactions of iron complexes with strong base and isopropanol were explored.The ³¹P{¹H}NMR spectrum of 5a showed only one set of a doublet at 48.9 ppm and 55.6 ppm with a J_PP coupling of 35.2 Hz.This indicated that5a has only one isomer.Similarly,5b has only one isomer in its ³¹P{¹H}NMR spectrum with chemical shifts at?85.73,69.67 ppm and a J_PP coupling constant of 31.4 Hz.The FT-IR spectrum of 5b exhibited a CO stretching frequency at 1900 cm^-1,indicating an electron-rich iron center in5b.The ⁵⁷Fe M?ssbauer spectrum of 5b afforded an isomer shift of 0.13 mm/s and a quadrupole splitting of 2.5 mm/s.This indicated the existence of a metal-ligand bonding covalency in 5b.the HOMO-1 of 5b contains 4.3%ene(amido)?*character,implying the presence of a?-backdonation interaction in 5b.This further proves the correctness and applicability of the new mechanism of organic-inorganic hybrid activation of the iron metal center.(3)Synthesis and application of chiral hybrid bisphosphinyl binaphthyl ligandsOn the basis of this activation mechanism,a diphosphine ligand containing an axial chiral binaphthyl amino(imine)structure was designed and synthesized to further improve the selectivity of the iron catalysts.In this process,a synthesis method of chiral hybrid diphosphine ligand was invented.Using chiral(R_A)-2,2'-dibromo-1,1'-binaphthyl as the starting material,the P?O group was successfully introduced into the axial chiral BINAP through the lithium halide exchange reaction and the oxidation reaction.Further,the chirality of the phosphine center was introduced by using the P?O group in the molecule as the inducing group.19 kinds(R_A)-2-phosphino-2'-phosphinyl-1,1'-binaphthyl ligands(10a-s)were prepared by flexibly adjusting the order of addition of substituents.The enantioselectivity of the ligands obtained was as high as 99%.There would be no racemization problem in the axial chirality during the synthesis process proved by high performance liquid chromatography.We reduced(R_A)-2-phosphino-2'-phosphinyl-1,1'-binaphthyl ligands by using the reduction system of triethylamine/trichlorosilane and cerium trichloride/sodium borohydride/lithium aluminum hydride.And the chiral configuration of the phosphine center is maintained during the reduction process.In addition,through the reduction reaction of the inversion of the phosphine center configuration,isomers with the opposite chirality of the phosphine center are obtained,which enriches the types of diphosphine ligands.The asymmetric hydrogenation of dialkyl ketones proves the potential application value of hybrid phosphine ligands and lays the foundation for the design and synthesis of iron catalysts with high selectivity and activity.