Asymmetric Organocatalytic Michael-Hemiacetalization Reaction Of β-nitroethanols And α,β-Unsaturated Aldehydes

The construction of N-substituted quaternary stereocenter is a very important and challenging task in asymmetric synthesis. Thus, the develpoment of efficient strategies to access N-substituted quaternary stereocenter is still a hot research topic. A Michael- hemiacetalization reaction ofβ-alkylβ-nitroethanols andα,β-unsaturated aldehydes was designed to formδ-lactols with a N-substituted quaternary stereocenter. To our delight, the product cis-δ-lactols precipiated from the reaction mixture stereoselectively and could be obtained with 53-79 % yield and 95-99 % ee by simple filtration and washing with chloroform. The recyclability of the catalytic system also was investigated. Due to the precipitation of cis-δ-lactols, the catalytic system was reused directly in next cycle after the filtrtion of cis-δ-lactols. To our pleasure, the catalytic system could be recycled for eight cycles without obvious deterioration in both enantioselectivity and yield. Then the synthetic versatility of cis-δ-lactols was explored. Cis-δ-lactones and tetrahydropyran with a N-substituted quaternary center, as well as 2,3-disubstituted prolinols, which were very valuable building blocks and ligands or catalysts in the synthesis of natural products and medicinal chemistry, could be easily synthesized from cis-δ-lactols.Unexpectedly, the absolute configuration of the stereocenter bearing the Ph group, which was determined by single-crystal X-ray analysis and NOE analysis, was opposite to that of the results obtained in other Michael addition of nitroalkanes toα,β-unsaturated aldehydes catalyzed by the same catalyst—(S)-diphenylprolinol silyl ether. To get insights into the reaction mechanism, the interaction between catalyst (S)-diphenylprolinol silyl ether and substrateβ-alkylβ-nitroethanols, as well as linear/nonlinear effect, were investigated. By NMR analysis, we discovered that catalyst (S)-diphenylprolinol silyl ether andβ-alkylβ-nitroethanols were able to form a tight complex. By linear/nonlinear effect analysis, we discovered a modest negative nonlinear effect. On the basis of these results, we proposed the two-moleclue participated catalytic model.