# Advances in Organic and Organic-Inorganic Hybrid Polymeric Supports for Catalytic Applications
## 3 Organocatalyst Asymmetric Reactions  
Organocatalysis is a useful synthetic method also applied in asymmetric reactions and polymer immobilization of chiral catalysts is still a topic of interest [46; 47]. In this section, one example of asymmetric \(\alpha\)-amination of 1,3-dicarbonyl compounds and some examples of C-C forming reactions including aza-Henry reaction, Michael addition, \(\alpha\)-alkylation of aldehyde, Diels-Alder reaction and aldol reaction, are reported. Finally, an example of the enantioselective flow synthesis of pyranonaphthoquinones is also described. In this contest, chiral supported organocatalysts based on bifunctional thioureas, a fluorinated amine, imidazolidinones, proline derivatives and a squaramide were examined. In 2015, the synthesis of polymer-supported bifunctional thiourea organocatalyst **56** and its application in the enantioselective \(\alpha\)-amination of 1,3-dicarbonyl compounds with azodicarboxylates were investigated (Scheme 24) [48]. Catalyst **56** was prepared in few steps from 4-amino-2-(trifluoromethylomethyl)benzoic acid avoiding the use of linkers/spacers. The Fmoc-protected amino acid **52** was immobilized onto a 1% DVB Merrifield resin, affording the material **53**, and successively was deprotected, achieving the PS-supported amino ester **54**. Then, the formation of the isothicyanate resin **55** and subsequent reaction with enantiopure (1\(R\),2\(R\))-2-(piperidin-1-yl)cyclohexylamine led to polymer-supported bifunctional thiourea organocatalyst **56**. Catalyst **56** was tested in the enantioselective \(\alpha\)-amination of a family of cyclic 1,3-dicarbonyl compounds with di-_tert_-butyl azo-dicarboxylate and diethyl azodicarboxylate. High yields and enantioselectivity values were obtained with 5 mol % of the bifunctional catalyst in toluene. Recycling experiments in the \(\alpha\)-amination of ethyl 2-oxocyclopentanecarboxylate with diethyl azodicarboxylate were carried out. High isolated yields and ee\({}^{\prime}\)s were consistently recorded over nine cycles, regenerating the catalyst with triethylamine after each run. The \(\alpha\)-amination of ethyl 2-oxocyclopentanecarboxylate with di-_tert_-butyl azodicarboxylate catalysed by resin **56** was also carried out in continuous flow. This experiment led to the desired product with 93% ee in 71% isolated yield with a productivity of 4.88 mmol\({}_{\text{prod}}\) mmol\({}_{\text{cat}}\)\({}^{-1}\).h\({}^{-1}\), a TON of 37 and the residence time of 21 min. **Scheme 24. Synthesis of organocatalyst **56** and its use in the enantioselective \(\alpha\)-amination of 1,3-dicarbonyl compounds. Novel bifunctional ureas and thioureas immobilized on sulfonylpolystyrene were prepared and used as recoverable and reusable organocatalysts in the stereoselective aza-Henry reaction under solvent-free conditions [49]. These catalysts (**62a-f**) were prepared by the synthetic strategy shown in Scheme 25. At first, the 1,2 diamines **58a-b** and the 1,6-diamine **58c** were synthesized starting from Boc-glycine and 6-(\(N\)-Boc-amino)hexanoic acid, respectively, by reaction with dibenzylamine or benzyl methylamine and successive reduction of corresponding amides **57a-c** with lithium aluminum hydride. Then, chiral triamines **60a-d** were obtained by reaction of L-valine with diamines **58a-c** or the commercially available 1,6-\(N\),\(N^{\prime}\)-dimethyl hexane diamine and sequential chemoselective reduction of the amide function with lithium aluminium hydride, followed by hydrogenolysis of the benzyl groups in case of amines **59a-c**. Chiral triamines **60a-d** were immobilized on sulfonylpolystyrene, affording materials **61a-d**. Finally, the deprotection with trifluoroacetic acid and the condensation with 3,5-bis(trifluoromethylomethyl) phenyl isocyanate or isothiamate led to supported ureas and thioureas **62a-f**. Optimization of the reaction conditions and screening of catalysts **62a-f** were studied in the reaction of \(N\)-Boc-benzaldimine with nitromethane.