Iron-Catalyzed Selective Aerobic Oxidation Of Alcohols

Oxidation is a fundamental transformation in chemistry. Oxidation of alcohols is the principal pathway to synthesize aldehydes/ketones. Traditionally, at least a stoichiometric amount of an oxidant, such as chromium oxide, DMSO or hypervalent iodine compounds, is required for these oxidations. However, the traditional methods may be facing many problems such as heavy metal pollution, expensive oxidants as well as inconvenient operation. Therefore, novel protocols using molecular oxygen as the oxidant is highly required. This dissertation mainly focuses on the iron-catalyzed selective oxidation of alcohols, which was successfully applied to the oxidation of various alcohols.We have taken allenols as standard substrates to investigate the catalytic aerobic oxidation of alcohols, and found that when Fe(NO3)39H2O/TEMPO was used as catalyst, the aerobic oxidation of allenols could be realized under the atmospheric pressure of oxygen at room temperature. However, the efficiency was obviously low, thus, we had to optimize the reaction conditions. Interestingly, when an inorganic chloride was added, the reaction efficiency was improved dramatically. It is worth noting that as a cheap kitchen chemical, sodium chloride, could also be used as the cocatalyst for this aerobic oxidation. Therefore, we defined Fe(NO3)3·9H2O/TEMPO/NaCl as the catalysts to study the scope of the substrates.Allenols:This catalytic aerobic oxidation could be applied to allenols conveniently, and the primary allenols could be selectively oxidized to aldehydes without over oxidation to carboxylic acids.Propargylic alcohols:Propargylic aldehydes or ketones, a classic of commonly used organic compounds, could be synthesized through such a catalytic aerobic oxidation protocol with high yields, a wide range of scope, and is potentially suitable for large-scale industrial production.Homopropargylic alcohols:When applied this aerobic oxidation to homopropargylic alcohols, the oxidation products with activated a-H could be isomerized to allenic ketones via column chromatography on silica gel; whereas those without activated a-H will not be isomerized during the column chromatography on silica gel.Allylic alcohols:we found geraniol could be oxidized to geranial through our protocol. It was observed that when this oxidation was carried out at a high concentration level, Z/E isomerization of the C=C bond was observed; the isomerization could be prevented at a lower substrate concentration level.Indole carbinols:Traditionally, these compounds could be oxidized to corresponding aldehydes or ketones with a large excess of MnO2. Such substrates could also be oxidized through our protocol with excellent yields.Benzylic alcohols and normal alcohols:Our protocol may also be applied to the oxidation of benzylic alcohols with excellent yields. It’s worth noting that when1-phenylethanol was used as the substrate for enlargement of the reaction scale, the catalyst loading may be reduced to1mol%each of Fe(NO3)39H2O, TEMPO, and NaCl, showing its high potentials for industrial production. For normal alcohols, this catalytic aerobic oxidation works smoothly to primary as well as secondly normal alcohols conveniently.Furthermore, we have optimized the solvent for the aerobic oxidation of propargylic alcohols, which may be suitable for industrial production.In conclusion, we have developed a Fe(NO3)39H2O/TEMPO/NaCl-catalyzed aerobic oxidation of alcohols with high efficiency, mild conditions, a wide scope of substrates, eco-friendly, and economic advantages, which could be applied in academic laboratories as well as industrial large scale production.