Intramolecular Ring-Closing Reaction Of Allyllic Azide Diazolates

Cyclopropane and morpholine-containing compounds have occupied an increasingly important position in the fields of pharmaceutical intermediates,fragrances,and cosmetics.Usually,these compounds are obtained through target-oriented directed synthetic strategies.In this thesis,starting from allyl azide diazolate compounds,selective synthesis of Cyclopropane compounds and morpholine ring compounds can be obtained under the control of optimized reaction conditions,via the diversity-oriented synthetic strategies.Using chiral ligands,two types of optically pure chiral compounds can be obtained with high enantioselectivity,which lays a solid foundation for the application of these compounds in related fields such as medicine and chemical industry.This thesis is mainly divided into the following three parts:1.Study on the synthesis and rearrangement equilibriating rate of allyl azide mixture.In this chapter,we synthesized three types of allyl azide mixtures:different aryl diazonates,different double bond phenyldiazonates,and different alcohol-based phenyldiazonates.The rearrangement rate of different double bond allyl azide mixtures and their analogs is relatively slow.In order to better develop the tandem reaction of such substrates,we used NMR tracking to study the rearrangement equilibrium rate of such substrates.2.The Cu/BOX system catalyzes the intramolecular asymmetric cyclopropanation reaction.In this chapter,we first explored the intramolecular ring formation of allyl azide diazotes catalyzed by different metals to obtain cyclopropanes and morpholine derivatives.It confirmed that copper catalysts are good to obtain cyclopropane with high chemoselectivity.Next,the chiral BOX ligands were further optimized,and finally the standard condition is developped as CuPF6(MeCN)4(5 mol%),(S,S)-Ph-BOX(6 mol%),NaBArF(6 mol%)in CHCl3 at room temperature to yield a cyclopropane product with high chemoselectivity and high enantioselectivity.Three types of substrates were expanded,and a series of chiral azidomethyl substituted cyclopropane products were obtained.A total of 17 compounds were synthesized with a chemical selectivity of up to 15:1 and a yield of 38%-69%with 79%-96%ee.An effective synthetic method is provided for the synthesis of chiral fully-substituted cyclopropanes.3.Intramolecular cyclization to synthesize morpholine derivatives.In this chapter,we expected to obtain morpholine derivatives with high enantioselectivity and high chemoselectivity through the regulation and screening of reaction conditions.On one hand,through the conditions of Cu(OAc)2(5 mol%),(S,S)-Me,Bn-Ph-Box(6 mol%),and NaBArF(6 mol%)in CPME in reflux,the morpholine derivatives with high enantioselectivity(>98%ee)were obtained by kinetic resolution.A total of 7 compounds were synthesized.The chemical selectivity was between 10:1 and 20:1,and the yield was about 5%with 10-98%ee.On the other hand,high chemoselectivity can be obtained by CuBF4(MeCN)4(5 mol%),(R,R)-inden-BOX(6 mol%),NaBArF(6 mol%),4? MS under MTBE reflux conditions to give morpholine derivatives.A total of 14 compounds were synthesized with chemoselectivities ranging from 1:1 to 1:2 and yields ranging from 13%to 31%,both types of compounds have no ee value.