| Oxazolidinone, thiophene thione, oxazolidine thione and camphor derivatives, such as chiral auxiliary reagents are widely used in the induction of asymmetric aldol condensation reaction, to obtain good asymmetric induction effect. Chiral hydatoin and cyclosulfonamide have many advantages as a kind of good chiral auxiliary reagents, such as the synthesis method is simple, the production is easy for separation and purification and the structural is stability, we applied it to asymmetric aldol reaction, the preparation of chiral carboxylic acids, and get a good asymmetric induction effect.First, preparation of chiral auxiliary reagents:Synthesis of chiral hydantoin via L-phenylpropanoid amino acid methyl esters and phenyl isocyanate returning in HC1solution to get5-benzylimidazolidine-2,4-dione, yield70%.Amino alcohols as the started material react with dimethylamino sulfonyl chloride under strong base, the product followed by reaction with p-TsCl. reaction of intermolecular ring-closure and then reaction with N-butylamine to obtain the wanted cyclosulfonamide. with a total yield of63.47%.Second, asymmetric aldol reaction:(S)-1-N-phenyl-3-benzyl-hydantoin and (S)-4-benzyl-1,2,5-thiadiazoline-1,1-oxide-cyclosulfonamide, under the condition of DMAP and triethylamine, acylation with propionyl chloride to obtain propionyl (S)-N-acylation product. Dibutyltin borate ester triflate as a lewis acid.DIPEA as a lewis base and the amount of1.2equivalent.0℃.(S)-N-propionyl hydantoin and (S)-N-propionyl cyclosulfonamide with seven kinds of aromatic aldehydes with different electrical generation to obtain (Syn, S, S) configuration of the aldol condensation product, the yield of the former83%to94%. the latter from85%to93%stereoselectivity of the former99:1-90:10, and the latter is99:1-92:8, with good asymmetric induction effect, initially speculated thehydantoin-induced aldol condensation reaction mechanism.Third, chiral auxiliary reagents relief: 0℃, THF/H2O as solution.(S)-N-propionyl hydantoin and (S)-N-propionyl cyclosulfonamide with aromatic aldehydes, asymmetric aldol condensation reaction product of1.05equivalent of hydroxidelithium and hydrogen peroxide under the conditions of easy relief to get the (2S,3S)-2-methyl-3-hydroxy-3-phenyl propionic acid, the former yield of92%. the latter yield was94%. chiral hydantoin and cyclosulfonamide can be recoveried quantitative, recoveries were higher than80%. the chemical configuration has not changed, with good stereoselectivity and chemical yield.Fourth, the structural analysis:NMR. infrared spectroscopy. mass spectrometry. optical rotation, photometry. elemental analysis, liquid chromatography. thin layer chromatography and other advanced analytical tools, testing and the data obtained and its structure is consistent with the reaction process and product.Chiral hydantoin and cyclosulfonamide used in asymmetric aldol condensation reaction, with good stereoselectivity and chemical yield is a good chiral induction reagents. |
