Catalytic Asymmetric Reversed Hydroboration Of Alkene

Chiral boronic esters are valuable synthetic intermediates which undergo a variety of stereospecific transformations.Methods to introduce the boronic ester moiety into organic molecules have attracted significant research interests.The transition metal catalyzed asymmetric hydroboration of alkenes is one of the most efficient and straightforward ways to prepare chiral boronic esters.However,the substrates are mostly limited to styrene or electron-rich alkenes.Catalytic asymmetric hydroboration of electron-deficient alkene is rarely reported.Hydroboration of electron-deficient alkenes faces several challenges.For example,hydroboration of ?,?-unsaturated carbonyl compounds usually results in the introduction of the hydride at the ? position and the boron at the ? position due to the electronic requirement.The ?-boryl carbonyl compound formed undergoes further hydrolysis to afford conjugated reduction product instead of borylation product.This selectivity has long impeded the development of the catalytic asymmetric hydroboration of electron deficient alkenes.This thesis aims at the development of asymmetric hydroboration of electron-deficient alkene through the design of ligand and catalyst.The thesis is divided into the following parts.(1)Rh-catalyzed reversed hydroboration to form vicinal stereocenters(Chapter 2).We have developed a Rh-based catalytic system that enables hydroboration of?,?-unsaturated carbonyl compounds occur with reversed selectivity for the first time.Specifically,Rh/Jo SPO catalyzed hydroboration of ?,?-unsaturated amides proceed smoothly with high level of regio-,diastereo-,and enantio-selectivities to provide hydroboration product with two vicinal stereocenters.Through the appropriate choice of substrate geometry(E or Z)and ligand enantiomer(R or S),all the possible diastereoisomers are readily accessible.Computational studies showed that Jo SPO ligand has a pronounced effect on the unusual selectivity of the hydroboration process.This strategy allows the access to a reversed hydroboration selectivity that has not been challenged before.(2)Rh-catalyzed reversed hydroboration to form quaternary stereocenter(Chapter3).Based on our previous work,we have developed a Rh-catalyzed asymmetric reversed hydroboration to synthesize chiral tertiary boronic eaters.Using a catalyst formed from cationic rhodium and DIOP ligand,hydroboration of ?,?-disubstituted?,?-unsaturated amides with unconventional selectivity to deliver chiral tertiary boronic esters in high regio-and enantioselectivity.This catalyst system works well for a range of functionalized substrates to generate useful chiral tertiary boronic esters.In summary,we have developed a new strategy to synthesize chiral boronic esters through catalytic asymmetric reversed hydroboration.Through this strategy,asymmetric reversed hydroboration of ?,?-unsaturated amides with various functional groups occur with high level of regio-and enantioselectivity to deliver boronic esters with two vicinal stereocenters,as well as a quaternary stereocenter(Chapter 3).Mechanistic studies have revealed the importance of ligand choice on the regioselectivity and enantioselectivity.Our work has changed the inherent regioselectivity for the hydroboration with?,?-unsaturated compounds,which led to synthetically useful hydroboration methods.