Fluorous solid catalyst

Fluorous solid catalyst 8 is highly effective for the Mukaiyama aldol reaction [Eq. (9)] and Sakurai-Hosomi allylation reaction [Eq. (lO)j. These reactions have been performed at -78 °C and room temperature, respectively, under heterogeneous conditions. Post-reaction, 8 has been recovered in high yield by decanting the liquids at room temperature. 

Fluorous ligands introduce an ease of purification in that the tagged phosphine ligand, the palladium catalyst complexed ligand, and the oxidized ligand can be completely removed by direct fluorous solid-phase separation (F-SPE) prior to product isolation. Similarly, an example of a fluorous palladium-catalyzed microwave-induced synthesis of aryl sulfides has been reported, whereby the product purification was aided by fluorous solid-phase extraction [91]. 

Fig. 3 Recycling of thermomorphic fluorous phosphine catalysts 5a,b via solid/liquid phase separations (Starting concentration of 2, 1.25 M cycle time, 8 h for 5a and 1 h for 5b)...

Fig. 7 Recycling of thermomorphic fluorous rhodium catalysts 16-Rf via solid/liquid phase separation...

Modified guanidines 3 efficiently catalyzed the asymmetric Michael addition of a prochiral glycine derivatives with acrylate, acrylonitrile and methyl vinyl ketone under simple and mild conditions. Remarkably, both product formation and enantioselectivity were dramatically improved using solvent-free conditions (Scheme 12) [34]. The addition of alcohols to methyl propiolate was performed using fluorous phosphines such as P[(CH2)2 (CF2)7 CF3]3 and again better yields of 99% have been obtained under solvent-free conditions. Toluene was added to efficiently separate the product from the solid catalyst, which was then reused without loss of activity [35],... 

Systems have been developed that allow the recycling of catalysts. The first case study involved simple adsorption of proline onto silica gel [6], but the system suffered from a loss in enantioselectivity. More recently, promising results have been obtained with fluorous proline derivatives [64] used for aldol reactions the recycling of fluorous catalysts has been demonstrated using fluorous solid-liquid extraction. Solid phase-supported catalysts through covalent bonds [65] and through noncovalent interactions [66] were also used for aldol reactions. Proline and other catalysts can be recycled when ionic liquids or polyethylene glycol (PEG) were used as reaction solvents [67]. 

Fluorous reverse-phase silica gel (separation by solid phase extraction). The hydroxyl residues on silica gel are modified with perfluoroalkyl chains. This causes a fluorophilic effect between the fluorous reagent/ catalyst/product and allows facile separation independent of temperature. 

Finally, the fluorous Cu-catalyst obtained from ligand 59 was recovered by simple evaporation of CH2CI2 followed by addition of cold hexane. Decantation of the liquid layer containing the products afforded a solid that could be reused without further addition of Cu source or ligand. The diastereoselectivities and enantioselectivities were maintained over five runs, although a slight decrease in chemical yield was observed. 

Liquid/Solid Catalyst-Reqrding Method without Fluorous Solvents... 

One way to conceptualize this phenomenon is to view the ponytails as short pieces of Teflon, which does not dissolve in any common solvent. As the ponytails become longer, some physical properties of the molecule approach those of Teflon. However, just as the miscibilities of fluorous liquid phases and organic liquid phases are highly temperature dependent, so are the solubilities of fluorous solids in fluorous or non-fluorous liquid phases. Hence, much higher solubilities can be achieved at elevated temperatures. This phenomenon can be used to conduct homogeneous reactions at elevated temperatures, with catalyst or reagent recovery by solid/liquid phase separation at lower temperatures. ... 

Bisprolindiamide 13a proved to be a good catalyst for the aldol reaction of cyclohexanone (57) with 4-nitrobenzaldehyde (2a) (Chart 3.6) [86, 33, 34] Carter et al. designed a proline sulfonamide-derivative possessing a long alkyl chain and applied it to the synthesis of 263 g of the aldol product anti-SSa [87]. Disappointingly, only 63% of the catalyst was recovered. To avoid this drawback, fluorous sulfonamide was synthesized and could be easily recovered from the reaction mixture by fluorous solid-phase extraction [88]. 

Diamine catalyst 10, which gives excellent results in the reaction of isobutyr-aldehyde with aromatic aldehydes, affords only moderate diastereoselectivity when used with aliphatic aldehyde donors [119]. Even C2-symmetric catalysts fail to give significant improvements [34c, 139]. Wang reported that the use of fluorous (5)-pyrrolidine sulfonamide 97 in such reactions give better diastereoselectivity and can easily be recovered by simple fluorous solid-phase extraction (Scheme 3.22) [122, 123]. 

Scheme 1.7 Synthesis of natural product-like molecules with unprecedented scaffold diversity. Initially, building blocks were added iteratively to a fluorous-tagged linker, with intermediates purified by fluorous-solid phase extraction. Metathesis cascades were used to reprogramme the scaffolds and to release final products from the fluorous-tagged linker. Reagents and conditions. (1) Grubbs first-generation catalyst, 21a 23% 21b 56% (2) fluorous-tagged Hoveyda-Grubbs second-generation eatalyst, 21c 33%.

Quinine decorated with a fluorous pony-tail (326) has been developed as a catalyst for the Michael addition of a-fluoro-/ -ketoesters ArC0CHFC02Et to A-substituted maleimides. The resulting products with two vicinal chiral centres were obtained with <87% ee and >20 1 dr, and the catalyst was recycled by fluorous solid-phase extraction. ... 

KOH treatment), or acids after (oxidation with KMnO ). All these transformations took place without decreasing the initial enantiomeric excess, showing the versatility of these compounds [128]. Recently, new fluorous (5)-pyrrolidme-thiourea recoverable catalyst 100 (10 mol%) has been allowed the synthesis of produets 96 in high yields (91-99%) and excellent enantioselectivities (85-92%), with the recovery of the catalysts being possible by fluorous solid-phase extraction [128]. 

Fluorous thiourea conveniently prepared by isothiocyanate perfluorooctyl aniline was also employed in chemoselective oxidation of the sulfide in the presence of 30% HjOj (Scheme 7.30) [46]. The catalyst could significantly shorten the reaction time and improve the product yield. As expected, the catalyst could be easily recovered by fluorous solid-phase extraction and reused for up to five times without significant loss of catalytic activity. 

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