A New Method Of Gold-catalyzed Synthesis Of Oxetan-3-ones

The application of oxetan-3-ones is very widespread, in organic synthesis and drug synthesis they are very important synthesis module. They have been incorporated into steroid skeletons, used to prepare oxetanocin derivatives, and converted into 3-aminooxetanes.However, existing synthesis methods typically demand multiple synthetic steps and highly functionalized substrate, the synthetic yield is low and the process need hazardousα-diazo ketones. This paper design a simple and efficient synthesis method, existing aldehyde or ketone as the starting material, reaction with alkyne obtain propargyl alcohol derivatives,then catalysis with organic gold catalysts and oxidation with pyridine N-oxides can get target product in high yield.Best effect oxidant and catalyst are selected to conver propargyl alcohol derivatives to oxetan-3-one derivatives. Dec-1-yn-3-ol as a substrate and PPh3AuNTf2 as gold catalyst to test the oxidation effect of different pyridine N-oxides,compare the yield of the product, secondary propargyl alcohols use 3-methoxycarbonyl-5- bromopyridine N-oxide as oxidant, tertiary propargylic alcohols use 4-acetylpyridine N-oxide as oxidant; Dec-1-yn-3-ol as a substrate and 3-methoxycarbonyl-5- bromopyridine N-oxide as as oxidant to test the catalytic effect of different gold catalysts, compare the yield of the product, secondary propargyl alcohols use, (2- biphenyl)Cy2PAuNTf2 as gold catalyst,tertiary propargylic alcohols use IPrAuNTf2 as gold catalyst.Aldehyde as the starting material, under the effect of n-butyllithium,react with (trimethylsilyl)acetylene,then tetrabutylammonium fluoride is added to get target products 1 and 4a~4f,yield 50%~73%;ketone as the starting material, under the effect of n-butyllithium and diisopropylamine, react with ethyl propiolate can get target products 6a~6f,yield 70%~78%.Synthetic secondary propargyls 1 and 4a~4f as raw material, (2- biphenyl)Cy2PAuNTf2 as gold catalyst, MsOH as acid, 1, 2-dichloroethane as solvent, 2,4-dichloro-N-oxide as oxidant, react at 30℃8h,get products 2 and 5a~5f,yield 52%~72%;synthetic tertiary propargyls 6a~6f as raw material, IPrAuNTf2 as gold catalyst, MsOH as acid, 1,2-dichloroethane as solvent, 2,4-dichloro-N-oxide as oxidant, react at 30℃8h,get products 7a~7f,yield 67%~78%.Through the above research,put forward a kind of need only two steps to transform aldehyde and ketone into corresponding oxetan-3-one derivatives. This paper seventeen oxetan-3-one derivatives are be synthesized, 1H NMR and 13C NMR were be used to characterize to confirm the products.