Study On Catalyzed Asymmetric Baeyer-villiger Reaction Of Cyclic Ketone By Using H₂O₂ As An Oxidant

As important organic synthesis products and intermediates,chiral lactones are widely used in drug synthesis,flavor synthesis and polymer monomer preparation,and as the most important core chiral frameworks of pharmaceuticals.Asymmetric Baeyer-Villiger oxidation reaction of cyclic ketone via chiral catalyst is the best method for the high-efficiency synthesis of chiral lactones.The traditional Baeyer-Villiger oxidation reaction has many disadvantages,such as more waste acid,low atomic utilization rate and the intractable by-products.In this paper,low-concentration hydrogen peroxide,which is environmentally friendly and easy to homogeneous reaction,is used as the oxidant.Three types of catalytic systems that can effectively catalyze asymmetric Baeyer-Villiger oxidation have been developed.The structure and thermal stability of the prepared catalysts were analyzed and tested by ~1H NMR,¹³C NMR,high-resolution mass spectrometry（ESI-MS）,FT-IR and thermogravimetric analysis（TG）.The three catalytic systems in this paper are as follows:（1）Chiral schiff base complexes catalyzed asymmetric Baeyer-Villiger oxidation reaction system of cyclic ketones:Cyclohexanediamine is used as chiral source to react with a variety of salicylaldehydes and their derivatives to synthesize ligands,and then react with a variety of coordination metal salts to synthesize a series of schiff base complexes,which are then applied to the asymmetric Baeyer-Villiger oxidation reaction of cyclic ketone.In this reaction,3-phenylcyclobutanone as template substrate,the best catalyst Co（Salen）-2 was selected by the experiments.At the same time,the influencing factors of the reaction were investigated.The optimum reaction conditions were as follows:n（3-phenylcyclobutanone）:n（catalyst）:n（H₂O₂）=1:0.1:12,25℃,6 h,1 m L deionized water as solvent,and the conversion of 3-phenylcyclobutanone could reach98.4%,the yield of 4-phenylbutyrolactone could reach 72.9%,and the ee value ofγ-phenylbutyrolactone was 58.9%.Under the optimum conditions,the universality of Co（Salen）-2 as a catalyst for the catalysis of a variety of other cyclones was investigated.The results showed that it had a good catalytic effect on small cyclones.（2）Ionic liquid supported schiff base complexes catalyzed asymmetric Baeyer-Villiger oxidation system of cyclic ketones:Starting from chloromethylation of salicylaldehyde derivatives,ionic liquid supported schiff base cobalt complexes were prepared by multi-step synthesis reactions.Using 3-phenylcyclobutanone as template substrate,the catalytic performance of this series of complexes for asymmetric Baeyer-Villiger oxidation was investigated.The best catalytic performance was Co-[Salen-Bim][Cl]₂.Then the influencing factors of the reaction were investigated.The optimum process conditions were as follows:n（3-phenylcyclobutanone）:n（catalyst）:n（H₂O₂）=1∶0.1∶9,reaction temperature 15℃,reaction time 8 h,1 m L deionized water as solvent.Under these conditions,the conversion of 3-phenylcyclobutanone was 95.8%,the yield ofγ-phenylbutyrolactone was 74.5%,and the ee%of lactone was 63.2%.The catalyst could be effectively recovered and recycled by simple washing and vacuum drying from aqueous phase after the reaction.The catalyst could be effectively recycled for more than 5 times.The results show that this catalyst has the better catalytic ability for small cyclic ketones under the optimum conditions by test.（3）Amino acid/Br（?）nsted acid DES catalyzed asymmetric Baeyer-Villiger oxidation system of cyclic ketones:A series of acidic DES were synthesized from a variety of chiral amino acids and a series of Br（?）nsted acids,and then applied to catalyze asymmetric Baeyer-Villiger oxidation of cyclic ketones.In the reaction with 3-phenylcyclobutanone as template substrate,the best catalyst L-Leu/4H₃PO₄was selected through experiments.At the same time,the influencing factors of the reaction were investigated.The optimum reaction conditions were as follows:n（DES）:n（H₂O₂）:n（substrate）=2.6:7:1,reaction temperature 25℃,reaction time 5 h.Under these conditions,the conversion of3-phenylcyclobutanone could reach 98.5%,the yield ofγ-phenylbutyrolactone could reach 78.1%,and the ee value could reach 69.2%.After the water phase was separated from the extractant,the catalyst could be effectively recovered and recycled after simple drying.The catalyst could be effectively recycled for more than 3 times.Under the optimum conditions,the universality of L-Leu/4H₃PO₄catalyst to catalyze a variety of other cyclic ketones was investigated.The results show that this catalyst has good universality for a variety of cyclic ketones.In general,the three kinds of asymmetric catalytic systems for Baeyer-Villiger oxidation reaction of 3-phenylcyclobutanone have showed better asymmetric catalytic activity.However,the catalysts in chiral schiff base complex catalytic system can not be recycled,while the catalysts in ionic liquid supported schiff base catalytic system can be recycled,but it has the disadvantage of complex synthesis.Amino acid/Br（?）nsted acid DES catalytic system not only has simple prepared catalysts but also is recyclable,which has great development prospects.This paper proposes a new idea for the design of asymmetric Baeyer-Villiger catalytic oxidation system,and provides a new green way for the efficient synthesis of chiral lactones.