Fluorous supports

In addition, a novel fluorous support has been developed recently as an alternative to traditional polymer supports and applied successfully to oligosaccharide synthesis in combination with the trichloroacetimidate method [541]. Each intermediate in the fluorous oligosaccharide synthesis [542,543] could be obtained by simple fluorous-organic solvent extraction, and the reactions could be monitored by TLC, NMR and MS, in contrast to solid-phase reactions. Moreover, the new liquid-phase technique is anticipated to be easily applicable to the large-scale synthesis. 

First Test System with Fluorous Support Leaching Data. 74... 

We sought to expand the range of catalysts and fluorous supports that could be applied in Fig. 1, and developed a surprisingly effective procedure involving common commercial Teflon tape. As described below, this provides not only a convenient means of catalyst recovery, but also of catalyst delivery. From an engineering standpoint, tapes offer a variety of unique attributes, and it is reasonable to extrapolate that meshes and/or reactor parts such as liners could be fabricated with similar properties. 

In conclusion, the new recycHng procedures described above offer virtually unhmited possibihties for optimization and catalyst engineering . The lengths and other structural features of the ponytails are easily varied. There are innumerable types of possible fluoropolymer supports, as well many additional classes of fluorous supports. Accordingly, a variety of further refinements and developments can be expected in the near future. 

Although the imidazolidinone catalysts used within these transformations are simple, cheap, readily accessible and in some cases recyclable using acid/base extraction, considerable efforts have been made to examine alternative methods to separate and recycle the catalyst with good success. Examination of the structure of imidazolidinone 22 shows two convenient points for the introduction of a polymer or fluorous support, R and R, both of which have been examined (Fig. 4). Curran has shown that identical reactivity, diastereoselectivity and enantioselectivity can be obtained using a fluorous tag (23) [53]. The catalyst can easily be recovered and recycled using F-SPE with excellent yield, purity and levels of activity. Polymer- (24) and silica-supported (25) imidazolidinones reported by Pihko [54] (R substitution)... 

In addition to the methods described above where the urea component is linked to a solid (or fluorous) support, it is also possible to link instead the acetoacetate building block to the solid support as shown in the example in Fig. 3.25 Thus, Biginelli condensation of Wang-bound acetoacetates with excess aldehydes (such as 2-trifluoromethylbenzaldehyde, Fig. 3) and urea/thiourea provides the desired DHPMs on solid support. Subsequent cleavage with trifluoroacetic acid furnishes the free carboxylic acids in high overall yields. 

Alternatively, an insoluble fluorous support, such as fluorous silica [43], can be used to adsorb the fluorous catalyst. Recently, an eminently simple and effective method has been reported in which common commercial Teflon tape is used for this purpose [44]. This procedure was demonstrated with a rhodium-catalyzed hydrosilylation of a ketone (Fig. 9.27). A strip of Teflon tape was introduced into the reaction vessel and when the temperature was raised the rhodium complex, containing fluorous ponytails, dissolved. When the reaction was complete the temperature was reduced and the catalyst precipitated onto the Teflon tape which could be removed and recycled to the next batch. 

Inazu has published details on the synthesis and use of three fluorous supports for peptide synthesis, the fluorous trialkoxybenzhydryl, Wang-type, and tert-butyl supports. The fluorous synthesis of Leu-enkephalin was later reported by the same group. 

Fluor OUS Sonogashira reactions (a) using a fluorous support and no fluorous solvent, (b) using perfluorodecaline under phosphine- and copper-free conditions. 

Oligosaccharide syntheses have also been performed in parallel using a fluorous support.A benzyl-type protecting group (HfBn) used in some of these procedures is shown in Figure 7.26. The novel approach here is that the fluorous group or tag is recycled and this can be achieved fairly easily... 

Miura, T., Goto, K. T., Hosaka, D. and Inazu, T. (2003) Oligosaccharide synthesis on a fluorous support. Angewandte Chemie International Edition, 42(18), 2047-2051. 

Some syntheses using intermediates with ionic-liquid tags have been reported, but they are not as versatile as solid or fluorous supports. The tagged intermediates and products are often isolated by precipitation and an advantage of ionic liquids is that the affinity and solubility of the tagged compounds can be altered by exchange of the associated anion. 

Scheme 8.54 Application of a fluorous-supported dienophile as a scavenger for dienes.

---