Asymmetric Mannich Reaction Catalyzed By Binuclear Zinc

Cyclic hydroxamate and pyridazinone are very important heterocyclic skeletons in organic synthesis,and exist in a variety of pharmacological and biologically active compounds.Therefore,there is great potential value in the field of organic synthesis.Synthesis of the pyridazinone has attracted people's long-term attention,but no method has been reported to synthesize chiral cyclic hydroxamate so far.This research work reported the asymmetric Mannich reaction of cyclic imines with ?,?-unsaturated ketones using dinuclear zinc complexes as catalysts for the first time.Through the selection and optimization of reaction conditions,various cyclic imines and ?,?-unsaturated ketones can be well adapted to this catalytic system.The reaction provides multisubstituted ?-amino ketones in 88%yields with diastereomeric ratio of>20:1 and enantioselectivities of up to 99%enantiomeric excess(ee).The reaction can be scaled up to the gram scale,and the reaction activity is almost unaffected.Through X-ray single crystal diffraction analysis of the product,the absolute configuration of the product,amino ketones was determined.Importantly,the product is very useful in organic synthesis.For example,it reacts with hydroxylamine or hydrazine under suitable conditions to synthesize chiral cyclic hydroxamate or pyridazinone derivatives,which is a new method to construct chiral cyclic hydroxamate and pyridazinone derivatives;In addition,the reduction of the product with sodium borohydride obtains chiral Tetrahydrobenzofuroxazine derivatives.