Transformation Of PMB Ethers Into Aehydes Or Ketones Via A New Tandem Deprotection/Oxidation Reation

2,3-Dichloro-5,6-dicyano-1,4-benzoquinone?DDQ?is a powerful oxidant in organic synthesis chemistry,which can effectively oxidize benzyl alcohol,heterocyclic aromatic alcohol or allyl alcohol to the corresponding aldehydes or ketones compounds.it is also a kind of strong dehydrogenation reagents which has widely applied in the oxidative deprotection of benzyl-type ethers and oxidative coupling reactions.2,2,6,6-tetramethylpiperidine N-oxy?TEMPO?is a mild oxidation catalyst,which can be oxidized the alcohols to the corresponding aldehydes or ketones.It has recently attracted significant interest in the oxidation of alcohols because of mild reaction conditions and high reactive activity,but it is unable to catalyze the oxidation of alcohols with molecular oxygen as the unique catalysts.So if we transfer molecular oxygen to the alcohol oxidation reaction,a co-catalyst in the catalytic system is requiredOur research group has developed DDQ/tert-butyl nitrite?TBN?catalyst system for the aerobic oxidation of alcohols and oxidative deprotection of p-methoxybenzyl?PMB?ethers in autoclave.In this dissertation,the application of DDQ/TEMPO/TBN/O₂ system was extended to the deprotection and oxidation of PMB ethers.Firstly,the DDQ/TEMPO/TBN/O₂ catalytic system was developed in the deprotection and oxidation of PMB ethers in autoclave.PMB ether of benzyl alcohol was selected as the model substrate to optimize the reaction conditions.We initiated this study by screening for the effect of solvent,the amount of catalyst,the pressure of the system,the reaction time and temperature on the catalytic system.Under the optimized reaction conditions,we then examined the substrate scope of different benzyl ethers or heterocyclic aromatic ethers.We can find that the reaction proceeded smoothly when substrates with electron-donating group.However,the reaction proceeded in the cost of increasing amount of catalyst and time when substrates with electron-withdrawing.Space steric hindrance of substituent also had a great effect on reaction.Secondly,we tried the newly established DDQ/TEMPO/TBN/O₂system for transformation of PMB ethers derived from aliphatic alcohols into their corresponding aldehydes or ketones.We initiated our investigation with PMB ether of 2-Octanol as model substrates to identify suitable reaction conditions.According to the experiment,the optimal reaction conditions are as follows:DDQ/TBN/TEMPO:3 mol%:10mol%:10 mol%.With the optimized reaction conditions in hand,most of substrates can be converted to corresponding product in high selectivity up to 95%.The PMB can be deprotected preferentially and then be oxidized to aldehydes or ketones in the presence of various hydroxyl-protecting groups.At last,the DDQ/TBN/TEMPO catalytic system is applied to synthetic of the drug intermediates indeno[1,2-c]isoquinolines.p-methoxybenzyl ethers was oxidized to aldehydes or ketones via a catalytic aerobic oxidation process,the advantage of this method improved the yield of this reaction and atom economy.