Recyclable Chiral Organocatalysts For Asymmetric Michael Additions

Recently, asymmetric Michael addition catalyzed by organocatalysts has received more and more attention. Organocatalysts present many advantages but also suffer from some problems, such as large dosage and unrecyclable, therefore, recycle of organocatalysts has become a research focus.In this paper, the recyclable organocatalysts reported recently were classified, and the progress of asymmetric Michael addition was reviewed.Based on the template reaction mechanism accepted generally, combined with our previous work, aiming to the defects of the reported catalysts, we designed and synthesized A1, A2, A3, A4 and A5 five catalysts. Their catalytic performance was also evaluated, in which A4 exhibited excellent catalytic performance. When employed in the asymmetric Michael addition of cyclohexanone with trans-β-nitrostyrolene, it could be recycled and reused for six runs. In the last run, it displayed 75% yield, 97:3 dr and 98% ee. Then, A4 was employed to catalyze the asymmetric Michael additions of ketones or aldehydes with nitrostyrolenes, and presented sixteen different γ-nitro carbonyl compounds with 67%-94% yields and good stereoselectivities(up to 99:1 dr and 98% ee). These results illustrated that A4 was a suitable catalyst for this type of reactions.With polyglycidyl methacrylate as a supporter, the immobilized catalysts B1 and B2 were designed and synthesized, and they were employed to catalyze the template reaction. Unfortunately, the results showed that B1 was invalid, and B2 only presented the product with 54% yield, 76:24 dr and 60% ee.Taking strong acidic cation exchange resin as a supporter, we designed and synthesized catalysts C1, C2 and C3. Their catalytic performances were evaluated by the template reaction. Fortunately, high yields(95%) and excellent stereoselectivities(97:3-98:2 dr, 90%-91% ee) were obtained, and they could be recycled for 3, 5, 16 runs respectively. Moreover, during this process, C2 and C3 did not lose their catalytic stereoselectivity. Then, using HPLC and straight line fitting method, it was found that there were 20.29% active components leaking from C1, and 5.42% from C2. However, there was almost nothing leaking from C3. These results adequately demonstrated that C3 was stable, while C2 took second place and C1 was the worst one. Thus, we could conclude that increasing the number of tertiary nitrogen-atom of organocatalyst indeed enhanced the affinity between resin and organocatalyst, and thus the stability of the catalyst was effectively improved.