Cyclizations Of Unsaturated Oximes Enable Synthesis Of Isoxazolines

Nitrogen-containing heterocyclic compounds play an important role in the field of organic synthesis.Particularly,isoxazoline as an important five-membered nitrogen-containing heterocyclic compound often exhibited Fungus,anti-cancer and anti-tumor drug activity,whichhas beenwidely found in some drugs,natural products and biologically active macromolecules.Many methods for the synthesis of isoxazolines have been well established.For example,the 1,3-dipolar cycloaddition reaction of nitrile oxides and olefins has been employed for the consrucction of isoxazoline backbone,albeit withpoor regioselectivity.Instead,using β,γ-unsaturated oxime as a key starting material can generate a verity of isoxazolines with different groups.A large number of studies show thatβ,γ-unsaturated oximes are usually used as intermediates or chiral ligandsin organic synthesis and some also have been investigatedfor cyclization reactions using transition metal catalysis or visible light catalysis.However,most of these reported cyclization reactionsstill require expensive transition-metalcatalysts(such as Pd,Ag,Ir,Ru,etc.)and critic reaction conditions such as high temperature and inert atomosphere.Therefore,the development of simple and efficient synthetic methods to construct isoxazoline skeleton is of great significance.Therefore,this thesis focuses on the development of green method toward the efficient construction isoxazoline and its derivatives,and which aredescribed as follows:1.Using cheap Fe(acac)2 as a catalyst,the radical cyclization of β,γ-unsaturated oximes and hydroxytoluenesulfonyl iodobenzene(Ph I(OH)OTs)can proceed under ambient conditionto generate a number of isoxazolesin high yields.This is a rare example of using Fe(II)–induced the C-I cleavage of hypervalent reagents(HIRs)to start a intramolecular radical cyclization of oximes,therefore achieving high regioselectivity.2.Using boron trifluoride etherate(BF3·OEt2)as a catalyst,a variety of oximes efficiently react with N-(arylthio)succinimides in 1,2 dichloridethane(DCE)at room temperature to afford the cyclization products in moderate to good yields.Initial experiments show that thecleavage of N-S bond of N-(arylthio)succinimides promoted by BF3 · OEt2 is a key to the cyclization of β,γ-unsaturated oximes,along with the formation of C-S bond.