Construction Of Chiral Seven-membered Lactams And Lactones Via Asymmetric Hydrogenation And Cycloisomerization

Recently,inspired by enzyme-catalyzed reaction models,researchers are in awareness of the importance of non-covalent interactions and have developed a series of chiral ligands based on them.The incorporation of synergistic effect between catalyst and substrate was helpful to low the kinetic energy barrows,accelerate reaction rate and improve reactivity and stereoselectivity.On basis of the non-covalent interaction of substrate and catalyst,we herein illustrate an example of asymmetric hydrogenation of(un)protected ?,?-unsaturated sevenmembered lactams.In addition,the lactones and their derivatives have been identified as an important kind of heterocyclic motifs,which are widely distributed in a large number of natural products and biologically active compounds.Moreover,these special skeletons are useful and versatile building blocks in organic synthesis.Based on the phosphine ligands commercially available,we successfully applied this system into the synthesis of a series of medium-sized lactones in extremely high regioselectivity with moderate yields.The detailed work is as follows:1.By the incorporation of the non-covalent interaction,we have successfully applied the Rh/Zhaophos system to the asymmetric hydrogenation of a series of(un)protected ?,?-unsaturated seven-membered lactams with good to excellent results(up to >99% conversions,99% yields,and >99% ee).Additionally,a series of control experiments were carried out to prove the pivotal role of hydrogen bonding effect in this reaction.2.Based on phosphorus ligands which are commercially available,we have successfully applied to the synthesis of a series of medium-sized lactones with good to moderate results(up to >99% conversions,68% yields,>99:1 rr,rr = regioselectivity ratio).The indole's derivatives can also be synthesized smoothly via this approach and excellent result was obtained(up to >99% conversion,75% yield,>99:1 rr,rr = regioselectivity ratio).