Tandem Reaction Of ?-Amido Sulfones:the Synthesis Of Chiral?-Amino Diesters And Axially Chiral Sulfone-Containing Styrenes

?-Amido sulfones as stable and easily prepared precursors of reactive N-protected imine derivatives are synthetic materials for many drug molecules and natural products,so it is widely used in organic asymmetric synthesis,especially in asymmetric Mannich reaction.However,the limited application of existing catalytic methods is mainly caused by the low atomic utilization of ?-amido sulfones since the sulfone groups are discarded in the form of metal sulfone salts after the reaction.In this study,the above problem was solved based on the waste-reuse strategy and our recent achievements on vinylidene o-quinone methide(VQM)intermediates.VQM intermediates are a class of compounds with multiple reaction sites and high reaction activity which can be generated through a prototropic rearrangement(tautomerization)of o-alkynylnaphthols under basic conditions.Based on our research on VQM intermediates,we found that the compound could react with benzene sulfinate anion by nucleophilic addition.Hence we designed a tandem reaction of Mannich and nucleophilic addition to make full use of ?-amido sulfones.After optimization of the reaction conditions,a series of chiral ?-amino diesters and axially chiral sulfone-containing styrenes were synthesized in good to excellent yields and stereoselectivities.Meanwhile,the reaction had good substrates universality.The electronic properties of the substituents did not show the significant impact on the reactivity or selectivity,especially the corresponding target products could also be obtained by the aliphatic substituted ?-amido sulfones with moderate yields and excellent stereoselectivities under this condition.To show the synthetic utility of this newly developed protocol,the anti-AIDS drug Maraviroc and trichloro derivatives were synthesized by ?-amino diester and axially chiral sulfone-containing styrenes,respectively.