The Asymmetric Allylboration Of Isatin Ketimines With Allylboronic Acids

Adjacent stereogenic centers,especially with a nitrogen-substituted quanternary carbon,are abundant in biologically active molecules and natural products.Development of new methods to construct such motif asymmetrically with readily available reagents is of particular importance and therefore highly demanded.Asymmetric allylboration of imines with ?-substituted allyl boron reagents,which can give direct access to chiral homoallylic amines with two adjacent stereogenic carbon centers,has received considerable attention and development.However,due to the lower electrophilicity of the carbon atom in the imine(C=N)comparing to the carbonyl(C=O)group,allylboration of imines especially ketimines is less developed than that of aldehydes or ketones.In this thesis,we have developed a highly efficient asymmetric allyboration of isatin ketimines with a wide range of nonchiral ?-monosubstituted allylboronic acids by using a chiral amino alcohol as the directing group under mild conditions in high yields(up to 92%)and with excellent diastereoisomeric ratios(up to 32:1).The control of stereoselectivity and enhancement of reactivity can be explained by the in situ formation of a boronate of the allylboronic acids with the amino alcohol moiety.Because of the cheap source of nitrogen and chirality,the high reactivity and the good control of diastereoselectivity,this metal-free methodology provides a practical solution to the preparation of 3-disubstituted aminooxindoles with an adjacent tertiary stereocenter.This newly developed method paves the base for the preparation of more complex derivatives and thus facilitates further biological studies.