Scheme12. At extile-supported organocatalyst for anhydride opening; MTBE = methyl tert-butyl ether.Scheme13. Organocatalytic aldolreaction conductedb yu sing the continuous-flow technique.Scheme11. PS-immobilized catalyst C32 for the amination of oxindoles 32.Scheme40. Photo-organocatalytic hydroxylation of ketoesters and amides. LED = light-emitting diode.Scheme41. Light-promoted cyclization.Scheme42. Light-promoted alkylation of aldehydes. EWG = electron-withdrawinggroup.Scheme49. Primary-aminec atalyzed light-promoted alkylations of dicarbonyl compounds.Scheme48. Light-promoted organocatalytic Michael additions.

Enantioselective organo-SOMO activation enables radical based functionalization of carbonyl compounds.

The catalytic efficiency of various aminesquaramides was tested in Michael/hemiketalization reactions of 4-hydroxycoumarines with two types of enones. Tertiary amine-squaramide organocatalysts afforded the best results regarding both activity and enantioselectivity when β,γunsaturated α-ketoesters were used as the Michael acceptors (yields up to 98%, enantioselectivities up to 90% ee). On the other hand, the primary amine-squaramides are the best choice for related reactions of 4-hydroxycoumarins with enones. The corresponding pyrano[3,2-c]chromen-5-on products were obtained in high enantiomeric purities (up to 96%). The Michael addition of 4-hydroxycoumarin to 4-phenylbut-3-en-2-on directly produced chiral anticoagulant drug (S)warfarin in 92% ee when green solvent 2-MeTHF and catalyst (S,S)-C8 were used. Moreover, an enantiomeric catalyst (R,R)-C8 gave (R)-warfarin in >99% ee.

Recent developments in organocatalysis have shown that these reactions can be advantageously performed in nonclassical media, such as ionic liquids or water. Among many organocatalysts, proline and its derivatives have attracted enormous attention, and these compounds have recently also been efficiently utilized in ionic liquids. Performing organocatalytic reactions in such media offer possibilities for easy catalyst recovery and reuse, on top of simplified product isolation.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

The enantioselective organocatalytic Michael addition in aqueous solution was compared with the reaction performed under solvent‐free ball‐milling conditions. A range of pyrrolidine‐derived organocatalysts were tested in the addition of aldehydes to nitroalkenes. Both procedures afforded good yields, diastereoselectivities, and enantioselectivities. The best catalyst in aqueous media was O‐lauroyl‐trans‐4‐hydroxyproline, whilst the ball‐milling technique was most‐efficient with α,α‐diphenyl‐2‐pyrrolidinemethanol trimethylsilyl ether.

Michael additions of malonodinitrile as well as several other reagents to chalcone have been found to proceed well in pure ionic liquids, without the addition of any catalyst. The catalytic effect of the residual acidity caused by hydrolysis of ionic liquids anions was excluded because HCl in dichloromethane did not catalyse the Michael addition of malonodinitrile. Piperidine was tested as the catalyst and was found to be a much better catalyst in ionic liquids than in dichloromethane. Therefore, the following question arose: what is the effect of ionic liquids on the dissociation constants of C--H acids?

Seventeen organocatalyts were tested for their ability to catalyst the addition of thiophenols to chalcones in [bmim]PF6. The products were isolated in high yield after a short reaction time, but no stereoselectivity was observed. The reactions also proceeded (without any stereoselectivity) in four other ionic liquids. In contrast, 16% and 26% ee were observed when L-proline and cinchonine, respectively, were used as the catalysts in CH2Cl2. Addition of thiophenols is also catalysed by HCl, as well as D-mandelic and L-tartaric acids. Addition of thiophenols to chalcones also occurred in neat ionic liquids, without any additional catalyst, but the rate of the reaction depended considerably on the structure of ionic liquid. The scope of the non-catalysed reaction in ionic liquids was tested by the reactions of 5 different thiols and 3 different alpha-enones.

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