Rhodium / Bisphosphine-thiourea Catalyzed Asymmetric Hydrogenation Of α,β-Unsaturated Compounds

Chiral compounds have a broad distribution in natural products and drugs.The transition metal-catalyzed asymmetric hydrogenation reaction can hydrogenate prochiral compounds such as ketones,imines and olefins in a chiral environment to obtain corresponding chiral alcohols and amine compounds.Compared with other types of asymmetric catalytic reactions,the reducing agent for asymmetric hydrogenation is green hydrogen,so the asymmetric hydrogenation catalyzed by transition metals is considered to be a direct,simple and high atomic economic method in asymmetric synthesis.Based on long-term research and exploration in the field of asymmetric hydrogenation,our group developed a new bifunctional bisphosphine-thiourea ligand(Zhao Phos).The bisphosphine moiety of the ligand can coordinate with the transition metal and the thiourea moiety can form a hydrogen bond or an ion pair with the substrate functional group to achieve activation of the substrate molecule,and assist in achieving an asymmetric hydrogenation process with high enantioselectivity and reactivity.On the basis of the preliminary work,we explored the adaptability of the transition metal/Zhao Phos system and successfully realized some asymmetric hydrogenation with important scientific research and application value substrates.The main contents can be divided into the following three parts:1)First,we used the Rh/Zhao Phos system to achieve asymmetric hydrogenation of a series of β-thio-α,β-unsaturated ester substrates.This new asymmetric catalytic methodology provided highly efficient access to two enantiomers of chiral organic sulfides ethyl β-substituted-β-thio-propanoates with excellent results(up to 99% yield and >99% ee for(Z)-substrates,up to 99% yield and 98% ee for(E)-substrates,TON up to 5000),which are important intermediates in organic synthesis.2)Subsequently,we applied the Rh/Zhao Phos system to β-boron-α,β-unsaturated ester substrates and achieved excellent results(up to 99% yield,99% ee,TON=2000).The chiral carbon-boron bond in hydrogenation products can be easily converted into carbon-oxygen and carbon-carbon bonds without losing enantiopurity;3)We have also successfully developed a Rh/Zhao Phos catalyzed asymmetric hydrogenation system for α,β-unsaturated sulfone substrates.This system has excellent selectivity for carbon-oxygen double bonds and carbon-carbon double bonds.It can selectively reduce the carbon-carbon double bonds in the substrate to obtain the target chiral product.Compared with the previous preparation method,our method has mild conditions,high atom economic efficiency,better results,and can be prepared in gram-scale.