Studies On The Direct Oxidative β-alkylation Of Secondary Alcohols Catalyzed By Iron

In organic synthesis, the most fundamental and extremely important method ofthe complex compound’s synthesis is a carbon-carbon bond. One of the methods ofthe carbon-carbon bond building is the alkylation reaction. The conventionalalkylating agents, such as alkyl sulfonates, alkyl halides, bring many byproductsafter the alkylation reaction, so it brings a great impact on the environment andreduces the atomic efficiency. For this reason, people began to explore the activatedalcohols, especially primary alcohols,as alkylating agent.However, there are still many deficiencies and shortcomings of the presentalkylation reaction to activate the primary alcohols as the alkylating agents:1)most ofthe catalysts are the noble transition metal catalysts such as Pd,Ru,Rh,Ir and so on,soit does not meet the sustainable development strategy;2) most of the catalysts are notcommercially available and need to synthesis in the laboratory, so they are notconducive to the further promotion and application of the method;3) the need to addcomplex ligands containning N or P,hydrogen donors and acceptors reduces theatomic efficiency and increases the difficulty of the after treatment;4)using a largeramount of base brings a great impact on the environment.There are few researches onthe direct oxidation β-alkylation of secondary alcohols now, among which there areonly two kinds of catalysts and both of them are noble metals:Pd and Ag. Using Pb asthe catalyst, the reaction not only needs to add a large amounts of hydrogen acceptor(1-decene), but also use a lot of base; the other kind of catalyst——Ag, isnot commercially available, and the reaction needs a high temperature to activate andhydrogenate this catalyst before use. Thus,the urgent needs of the new catalysts,especially the inexpensive metal catalysts, has become a major problem faced bychemists.The laboratory used the iron catalysts for the direct β-alkylation of secondaryalcohols with the primary alcohols for the first time in the world，and it has many advances:1)using the cheap metal iron first time,which is commercially;2)only use acatalytic amount of base;3)no complex ligands containning N or P,or hydrogen donor(acceptor), overcome many disadvantages in this kind of reaction in the past. Basedon our preliminary studies, we use the iron catalyst——Ferrous acetylacetonate forthe direct oxidative β-alkylation of secondary alcohols.The studies found that thiscatalyst can also catalyze the direct β-alkylation of secondary alcohols.Thesealkylation works provide a new catalystic system to works as a new cheap alternativesfor the precious transition metal catalysts. These studies also allow us to have adeeper knowledge and understanding on the iron-based catalysts.At first, on the base of our preliminary studies, we used the ferrousacetylacetonate in the direct oxidative β-alkylation of secondary alcohols reaction.Weselected the optimum conditions of the model reaction in which the1-phenylethanoland benzyl alcohol were used as the substrates. Then we studied the substrate scope ofthe catalytic and obtained nine higher ketone products in high yields. This study is thefirst time to use the iron-based catalysts for the direct oxidative β-alkylation ofsecondary alcohols.It is also for the first time to supply the low-cost metal catalystsystem as a new alternative towards the noble metal catalysts in this kind of alkylationreactions.In the experiment, we also found that the main product was gradually changed tothe higher alcohol with the amount of the solvent increasing in the above reaction.Only by changing the amount of the solvent, the product selectivity can be changedstill under the air atmosphere. We also did some experiments about the substratescope and have an exciting results. This research shows the cheap metals, especiallythe iron catalysts, have the broad potential in the application and developmentprospect on the alkylation of secondary alcohols reaction.Both of the two reactions are single-step reactions.The low cost ferrous catalyst,using of a catalytic amount of a base, no adding any hydrogen donor or acceptor,andcarrying out in the air are greatly reducing the reaction cost, improve the atomutilization, and have much less impact on the environment.It can greatly meet with therequirements of the green chemistry. Our studies can not only further deepen our understanding on the iron-based catalysts, but also further expand the application ofiron-based catalyst in the organic synthesis reaction.