Noncovalent Interactions In Rh-Catalyzed Asymmetric Hydrogenation Of Functionalized Olefins

Transition metal-catalyzed asymmetric hydrogenation which transforms achiral unsaturated compounds,such as olefin,ketone or imine into corresponding chiral compounds has been considered as a direct,environmental compatibility and atom economic method in asymmetric synthesis and exhibited great application prospects in industrial production.In recent years,inspired by enzymatic catalysis,researchers found that catalysis by capable of binding and activating substrates solely via noncovalent interactions including noncovalent ion-pair interaction and H-bonding,can obviously improve the reactivity and stereoselectivity.This has emerged as an important napproach in organosythesis.Herein,it will play an important role not only in the rate acceleration,through lowering the kinetic energy barrows,but also in stereoselectivity improvement by suppressing the degree of freedom in the transition state if we applied the noncovalent interactions into asymmetric hydrogenation.On the basis of this theory,this paper explained an important role of nonovalent interactions in Rh/Wudaphos-catalyzed asymmetric hydrogenation of 1,1-substituted ethenylphosphonic acids/sulfonic acids and Rh/Zhaophos-catalyzed asymmetric hydrogenation of benzo[b][1,4]dioxine derivatives.The detailed works are as follows:(1).Based on our previous investigation of ferrocenyl chiral bisphosphorus ligands Wudaphos and SPO-Wudaphos in the application of asymmetric hydrogenation of unsaturated acids via noncovalent ion pair interaction,we herein successfully introduce this interaction in the asymmetric hydrogenation of 2-substituted ethenylphosphonic acids under base-free and mild conditions,providing various chiral phosphonic acids with excellent reactivities and enantioselectivities for the first time(14 examples,>99%Conv.;ee up to 98%,TON up to 2,000).Importantly,control experiments showed that the attractive noncovalent ion-pair interaction between the ligand and ethenylphosphonic acid substrates played a critical role in achieving high reactivity and excellent enantioselectivity in this asymmetric hydrogenation.(2).In the present work,this novel noncovalent ion-pair interaction activation strategy was proved to be very efficient in Rh/Wudaphos-catalyzed asymmetric hydrogenation of various ?-arylethenylsulfonic acids formed in situ from sodium a-arylethylsulfonates using CF3SO3H.A series of sodium a-arylethenylsulfonates bearing different substituent groups on the phenyl ring were hydrogenated well to afford the corresponding chiral ?-arylethylsulfonic acids with full conversion and good to excellent enantioselectivity(>99%Conv.;up to 96%ee).Moreover,was hydrogenated well on a gram scale under the optimized reaction conditions,the desired product was obtained with 99%conversion and 92%ee.Finally,control experiment results demonstrated that the non-covalent ion pair interaction between the a-arylethenylsulfonic acid and the Wudaphos ligand plays a critical role in obtaining high reactivity and excellent enantioselectivity in this asymmetric hydrogeanation.(3).On the basis of H-bonding interaction,this work successfully applied a bisphosphine-thiourea ligands(ZhaoPhos and N-Me-Zhaophos)into the Rh-catalyzed asymmetric hydrogenation of various benzo[b][1,4]dioxine derivatives.Excellent reactivities and enantioselectivities were achieved in the asymmetric hydrogenation of these substrates utilizing Rh-Zhaophos or N-Me-Zhaophos(up to 99%yield,>99%ee,TON up to 24,000).Moreover,highly efficient and creative synthetic routes for the construction of some important biologically active molecules,such as(R)-Doxazosin,BSF-190555,WB4101 and MKC-242,were successfully developed through this powerful asymmetric hydrogenation methodology.