[organic] angelw: Iron catalyzed C-O / C-O closed-loop metathesis of fatty ether

The complex decomposition of multiple bonds is one of the most interesting reactions in organic synthesis Among them, the closed-loop metathesis of alkyne and alkyne has become a powerful tool for the synthesis of small, middle and large rings Recently, Schindler and Li reported the closed-loop metathesis of olefins and carbonyls catalyzed by iron respectively This method has been applied to the synthesis of conjugated materials and unsaturated heterocycles (scheme 1) However, the complex decomposition reactions involving single bond, especially C (SP 3) - x bond, are rarely reported The reason lies in the competitive elimination of β - hydrogen and the higher energy barrier of oxidative addition reaction Recently, Dr bill Morandi of Max Planck Institute of coal research in Germany reported for the first time the closed-loop C-O / C-O decomposition reaction of aliphatic diethyl ether catalyzed by iron, which provided a new way for the synthesis of tetrahydrofuran, tetrahydropyran and morpholine compounds (angel Chem Int ed 2018, DOI: 10.1002/anie.201802563) (source: angelw Chem Int ed.) firstly, the author selected the reaction conditions with 1,5-dimethoxypentane (1) as the substrate (Table 1) 20 mol% Fe (OTF) 3 can be used as Lewis acid catalyst to obtain the target product in 85% yield Other weakly coordinated MX3 salts, such as AlCl3, SC (OTF) 3, FeCl3 and Febr, have different catalytic properties The results of solvent screening showed that strong coordination solvent (acetonitrile, chloride solvent) was not conducive to the reaction (source: angelw Chem Int ed.) then, the author studied the substrate application range of the reaction (Table 2) Five and six membered cyclic ethers can be selectively synthesized by adjusting the length of the chain The aromatic ring containing fluorine, chlorine, bromine, methoxy, trifluoromethyl and other substituents in the substrate can decompose smoothly The target product can also be obtained in good yield from the three functional groups containing large steric hindrance It is worth noting that the reaction can be used in the synthesis of bridged and spiro compounds, which shows its great potential in drug development In addition, the reaction is also suitable for the synthesis of dioxane and morpholine compounds (scheme 2) (source: angelw Chem Int ed.) (source: angelw Chem Int ed.) later, the author studied the reaction mechanism of this kind of closed-loop complex decomposition reaction (scheme 3) The by-product dimethyl ether in the reaction system was detected by GC-MS, and it was further proved that the gas-phase dimethyl ether was not the driving force for the forward reaction, and the reaction was not reversible (source: angelw Chem Int ed.) in addition, the author found that compound 26 can interact with Fe (OTF) 3 and naome to obtain the target product, and compound 1 and compound 8 can react in the same reaction system to obtain the cross product, which indicates that the reaction undergoes a bimolecular reaction mechanism (scheme 4) When AlCl3 is used instead of Fe (OTF) 3, the formation of 1-chloropropane can be detected It is proved that the cyclic onium ion is the intermediate of the reaction (source: angelw Chem Int ed.) based on the above experimental results, the author proposed the possible mechanism of the reaction, as shown in Figure 5: Fe (OTF) 3 forms Lewis acid-base adduct 34 with ether oxygen atom first; then the non coordinated oxygen atom undergoes intramolecular nucleophilic attack to obtain cyclic oxygen intermediate 26 and Fe ome complex 27; finally, 26 Tetrahydropyran (2) and dimethyl ether (3) were obtained by demethylation (source: angelw Chem Int ed.) conclusion: Dr bill Morandi of Max Planck Institute of coal research in Germany reported for the first time the closed-loop C-O / C-O metathesis of aliphatic diethyl ether catalyzed by iron, which provided a new way for the synthesis of tetrahydrofuran, tetrahydropyran and morpholine compounds The mechanism study shows that the reaction is carried out by the catalysis of easylic acid, and the cyclic oxygen onium is the key intermediate of the reaction In addition, this reaction provides a new idea for the development of new complex decomposition reactions involving inert C (SP 3) - x bonds.