Catalytic Asymmetric Tandem Conjugate Addition Addition-protonation Reactions To Install Nonadjacent Chiral Secondary Hydroxyl

The first asymmetric tandem conjugate addition-protonation to methylene 1,3-oxazolidine-2,4-diones has been developed.By using readily prepared L-amino acid-based urea-tertiary amine catalysts,the reactions with 3-oxindoles,thiols and 5H?oxazol?4?ones as nucleophiles afforded three series of protonation products in high yields with excellent stereoselectivities,thus introducing either an all-carbon quaternary stereocenter,sulphur and a heteroquaternary stereocenter at the nonadjacent position of chiral secondary hydroxyls,respectively.The success of current strategy should provide a general and efficient approach for the synthesis of valuable chiral secondary hydroxyls with diverse nonadjacent functional groups.1.Asymmetric Conjugate Addition-Protonation of 3-Oxindoles to Methylene 1,3-Oxazolidine-2,4-dionesGiven 3,3-disubstituted oxindoles with a quaternary carbon stereocenter behaving as the nonadjacent functional groups of chiral secondary hydroxyls,we were attracted to probe the feasibility of asymmetric tandem conjugate addition-protonation of 3-oxindoles to methylene 1,3-oxazolidine-2,4-diones,The outcomes revealed that L-tert-leucine derived tertiary amine-urea was most suitable catalyst,leading to 3a in 97% yield with 98% ee with >20:1 dr.2.Asymmetric Conjugate Addition-Protonation of Thiols to Methylene 1,3-Oxazolidine-2,4-dionesInspired by the success,we next performed tandem conjugate addition-protonation of thiols to methylene 1,3-oxazolidine-2,4-diones,to evaluate the feasibility of this strategy in the installation of sulphur,as the representative of heteroatoms,at the nonadjacent position of chiral secondary hydroxyls.By changing the substituent of urea,the present protocol was leading to products in 84-98% yield with 95%->99% ee.3.Asymmetric Conjugate Addition-Protonation of 5H?oxazol?4?ones to Methylene 1,3-Oxazolidine-2,4-dionesBy changing the substituent of urea,we next performed tandem conjugate addition-protonation of 5H?oxazol?4?ones to methylene 1,3-oxazolidine-2,4-diones,the present protocol was leading to products in 80-98% yield with 81-95% ee.75:25-87:13 dr.