TiCl 4 -chiral Phosphoramide Catalyzed The Intermolecular Asymmetric Hydrogen Alkoxylation Of Non-activated Olefins

Tetrahydrofurans are important structural motifs of biologically active natural products and pharmaceuticals.The intramolecular hydroalkoxylation of unactivated alkenes is an attractive strategy for constructing tetrahydrofurans,which is atom economical because it enables the construction of cyclic ethers from the corresponding acyclic hydroxyl alkenes with 100% atom efficiency.Despite the current progress in the area of asymmetric hydroalkoxylation,there is still considerable room for the improvement in terms of reactivity and enantioselectivity.Enlightened by Lewis Acid Assisted ChiralBr?nsted Acid,we developed the catalytic system of asymmetric hydroalkoxylation with titanium based on chiral N-triflyl phosphoramide ligand.The studies include the following several respects.(1)Various chiral N-triflyl phosphoramide ligands have been synthesized and were successfully used in asymmetric intramolecular hydroalkoxylation of unactivated alkenes.(2)With the best chiral N-triflyl phosphoramide ligand in hand,the reaction parameters including solvent,additive,the range of coordinational metals,source of titanium were systematically investigated to get the optimal conditions for the asymmetric hydroalkoxylation.(3)Under the optimized reaction conditions,substrate scope for the asymmetric hydroalkoxylation of unactivated alkenes was then examined in the presence of chiral N-triflyl phosphoramide.A variety of chiral tetrahydrofuran derivatives were obtained with yields of up to 99% and in up to 71% ee.(4)Some plausible mechanisms have been proposed for the titanium-chiral N-triflyl phosphoramide-catalyzed intramolecular asymmetric hydroalkoxylation of unactivated Alkenes.