Asymmetric Conjugate Addition-Protonation Reaction Of 2,2'-Biphenol-Induced Diastereoselective Switch

Asymmetric protonation is an effective method for constructing chiral tertiary carbon.The specific process is to transfer hydrogen proton to carbanion under the action of chiral control.In order to introduce functional groups at nonadjacent position of different chiral tertiary carbons,a conjugate addition-protonation reaction is required.Therefore,this paper outlines the asymmetric conjugate addition-protonation of 5H-oxazole-4-ones and 5-methylene-1,3-oxazolidine-2,4-diones using amino acid-derived urea as a catalyst.Chiral molecules with multiple stereocenters are widespread in nature and medicines.Asymmeric catalysis has allowed the formation of a chiral molecule's enantiomers with equal ease by applying the enantiomeric pair of a chiral catalyst.However,the diastereodivergent synthesis is a great challenge.In most reactions,the formation of one of the diastereomers is inherently preferred,while the formation of another diastereomer is not direct.On this basis,we screened the designed reaction with a series of conditions such as catalyst,solvent,reaction temperature,and additives.In the end,not only a series of chiral conjugate addition-protonation products were obtained,but also it was found that when 2,2'-biphenol was used as an additive,the corresponding diastereomers could be obtained.A synthetic strategy for catalytic asymmetric conjugate addition-protonation and diastereoselective switch between 5H-oxazol-4-ones and 5-methylene 1,3-oxazolidine-2,4-diones was established.An array of chiral conjugate addition-protonation products bearing 1,3-O-heterotertiary-O-heteroquarternary nonadjacent stereocenters were obtained in excellent yields,moderate to good diastereoselectivities,and excellent enantioselectivities(up to 97% yield,11:1 dr,and 98% ee).Induction by 2,2'-biphenol could effectively promote the production of the corresponding diastereoisomers via cycloaddition intermedia,all design substrate types can achieve satisfactory stereoselective results.The experiment of magnification also proved the practical application value of this strategy we designed,and the absolute configuration was analyzed by X-single crystal diffraction and two-dimensional spectroscopy.Four configurations of isomers(S,S),(R,R),(S,R),(R,S)were obtained.