Soluble supports high loading

By replacing insoluble cross-linked resins with soluble polymer supports, the well-estabhshed reaction conditions of classical organic chemistry can be more readily apphed, while still fadhtating product purification. However, soluble supports suffer from the hmitation of low loading capacity. The recently introduced fluorous synthesis methodology overcomes many of the drawbacks of both the insoluble beads and the soluble polymers, but the high cost of perfluoroalkane solvents, hmitation in solvent selection, and the need for specialized reagents may hmit its apphcations. 

Furthermore, polymer-assisted solution-phase syntheses also show several advantages over Merrifield-type syntheses. Fxcept for some industrially employed heterogeneous catalysts the requirement of high loading capacities for the sohd supports is not necessarily of prime importance for immobilized catalysts. Because not every site needs to react, lower loadings are acceptable. The recovered catalyst is often available for immediate reuse. A discussion on immobilized catalysts should also include a brief listing of obstacles associated with their use, particular in comparison to their soluble analogs ... 

Parquette et al. reported on a disaccharide synthesis on a hyperbranched polyester support (Boltorn hyperbranched polymer) (16) (Fig. 7.9) [44]. This polymer was obtained in a one-step synthesis and offers low cost, high-loading capacities (8.8 mmol OH-groups g ), and the intermediates were soluble in most aprotic solvents. 

Dendrimers, among other applications, are generating interest as soluble supports thanks to the following intrinsic characteristics (i) the well-defined molecular composition of a dendrimer provides a support with a precisely defined arrangement of the reactive sites, (ii) a high loading of reactive sites is achieved on the dendrimer surface and (iii) nanofiltration techniques are available to separate the dendritic support from products. Dendrimer 143, based on a carbosilane core, possesses 12 ester functionalities on... 

The class of so-called soluble supports, including PEGs, non-cross-linked PS, and the recently introduced high-loading dendrimers, will be covered in Section 8.5. 

Soluble PEG supports have been used for different applications such as the synthesis of peptides (241, 245) and peptidomimetics (246) soluble-supported catalysts (247-249), reagents (250-253), scavengers (254), and traceless linkers (255-257) to improve purification protocols (258, 259) and high-loading PEG-derived soluble supports (260), particularly in the synthesis of arrays of small organic molecules (261-275). Several recent reviews (276-281) illustrate their usefulness but also show how additional efforts could make PEG liquid-phase combinatorial synthesis more reliable. 

Further development of reliable, high-loading soluble supports with complementary solubilizing properties and with high stability to organic reaction conditions can be expected. An intriguing tme combinatorial approach to the optimization of the physico-chemical properties of soluble supports has recently been reported by Gravert et al. (287) and is described in Section 11.3.2. 

The combinatorial assembly of isocyanate-decorated dendrimers was reported by Newkome et al. (93) as a method to modulate the solubility, reactivity and viscosity properties of such popular materials. This modulation has an obvious impact for the discovery of high loading, soluble and flexible supports for high throughput organic synthesis. 

Some examples in the literature explore the use of ILs as soluble supports a new type of hydrolytic ionic liquid based on fructose was developed and used for Diels-Alder and transesterification reactions [80-82]. The advantages are the timable miscibility and the high loading capacity compared to other soluble supports such as PEG. 

If catalysts with high loadings of the active compounds are to be made, limited solubility of the precmsor compoimd may cause problems, and multiple impregnations may have to be applied. With incipient wetness impregnation, even precursor com-poimds which do not interact with the support can be deposited when the solvent is removed during a subsequent drying procedme. This can be illustrated with Figure 6-4. 

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