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Glycerol carbonate is a useful compound of value for a variety of cosmetic, material, and synthetic applications. Its synthesis relies either on the carbonation of glycerol or the conversion of gly...

Although organometallic chemistry has been the predominant category for the preferred catalytic transformations applied in pharmaceutical industry since the nineteenth century, during the last 20 years, organocatalytic processes are becoming more common and of wide use in drug discovery field. In particular, enantioselective organocatalysis is emerging as one of the main tools and a greener protocol for the synthesis of chiral molecules. As for today, the main applications of chiral enantiopure compounds are in the pharma and fine chemicals industries, in crop protection, and in the biotechnology area.

α,α-Diphenylprolinol methyl- and trimethylsilyl ethers anchored onto a polystyrene resin have been prepared by a copper-catalyzed azide-alkyne cycloadditions (CuAAC). The catalytic activity and enantioselectivity displayed by the O-trimethylsilyl derivative are comparable to those exhibited by the best known homogeneous catalysts for the addition of aldehydes to nitroolefins and of malonates or nitromethane to α,β-unsaturated aldehydes. The combination of the catalytic unit, the triazole linker, and the polymeric matrix provides unprecedented substrate selectivity, in favor of linear, short-chain aldehydes, when the organocatalyzed reaction proceeds by an enamine mechanism. High versatility is noted in reactions that proceed via an iminium ion intermediate. The catalytic behavior of polystyrene-supported α,α-diphenylprolinol methyl ether was also evaluated in asymmetric Michael addition reactions. As a general trend, the CuAAC immobilization of diarylprolinol ethers onto insoluble polystyrene resins offers important operational advantages, such as high catalytic activity, easy recovery from the reaction mixture by simple filtration, and the possibility of extended reuse.

A polymer-supported α,α-diarylprolinol silyl ether displays catalytic activity and enantioselectivity comparable to the best homogeneous catalysts in the Michael addition of aldehydes to nitroolefins. Above all, the combination of polymer backbone, triazole linker, and catalytic unit confers to it an unprecedented substrate selectivity in favor of linear, short-chain aldehydes.

Enantiopure trans-triflate-silyloxypyrrolidine efficiently catalyzes the asymmetric α-aminoxylation of aldehydes (I) with nitrosobenzene (II).

A polymer-supported α,α-diarylprolinol silyl ether displays catalytic activity and enantioselectivity comparable to the best homogeneous catalysts in the Michael addition of aldehydes to nitroolefins. Above all, the combination of polymer backbone, triazole linker, and catalytic unit confers to it an unprecedented substrate selectivity in favor of linear, short-chain aldehydes.

The fast and highly stereoselective Mannich reaction of aldehydes and ketones with the N-(p-methoxyphenyl) ethyl glyoxylate imine catalyzed by polystyrene resins functionalized with (2S,4R)-hydroxyproline is reported. The effect of the nature of the linker connecting proline with the polymeric backbone has been studied, and a 1,2,3-triazole linker constructed from azidomethyl polystyrene and O-propargyl hydroxyproline turns out to be optimal for catalytic activity and enantioselectivity. With aldehyde donors, fast reactions leading to complete conversion in 1-3 h are recorded in DMF. With ketone donors, the reactions tend to be slower, but can be efficiently accelerated (six-membered ring cycloalkanones) by low-power microwave irradiation. This approach, which greatly facilitates product isolation since the catalyst is removed by simple filtration, has allowed the implementation of the reactions of aldehyde substrates in a continuous-flow, single-pass system. In this manner, the continuous synthesis of the enantiomerically and diastereomerically pure adducts (syn/anti>97:3; ee>99 %) has been achieved at room temperature with residence times of 6.0 min. This methodology has allowed for the preparation of up to 7.8 mmol of the desired Mannich adduct through the use of 0.46 mmol of catalytic resin (5.9 mol %), in a greatly simplified experimental protocol that avoids purification steps.

The fast and highly stereoselective Mannich reaction of aldehydes and ketones with the N-(p-methoxyphenyl) ethyl glyoxylate imine catalyzed by polystyrene resins functionalized with (2S,4R)-hydroxyproline is reported. The effect of the nature of the linker connecting proline with the polymeric backbone has been studied, and a 1,2,3-triazole linker constructed from azidomethyl polystyrene and O-propargyl hydroxyproline turns out to be optimal for catalytic activity and enantioselectivity. With aldehyde donors, fast reactions leading to complete conversion in 1-3 h are recorded in DMF. With ketone donors, the reactions tend to be slower, but can be efficiently accelerated (six-membered ring cycloalkanones) by low-power microwave irradiation. This approach, which greatly facilitates product isolation since the catalyst is removed by simple filtration, has allowed the implementation of the reactions of aldehyde substrates in a continuous-flow, single-pass system. In this manner, the continuous synthesis of the enantiomerically and diastereomerically pure adducts (syn/anti>97:3; ee>99 %) has been achieved at room temperature with residence times of 6.0 min. This methodology has allowed for the preparation of up to 7.8 mmol of the desired Mannich adduct through the use of 0.46 mmol of catalytic resin (5.9 mol %), in a greatly simplified experimental protocol that avoids purification steps.