Resin supports

Lightly crosslinked resins are less robust but have greater ability to swell in appropriate solvents. Typically a 1-2% crosslinked divinyl benzene polystyrene resin is employed in organic synthesis. 

An extensive list of the commercially available resins is available from Sigma-Aldrich (www.sigmaaldrich.com), Novabiochem (www.novabiochem.com), Fluka and other chemical companies. Sigma-Aldrich and Novabiochem have excellent catalogs. In addition, the Novabiochem catalog and website are a rich source of useful technical information. 

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Y. Bing, Monitoring the Progress and the Yield of Solid Phase Organic Reactions Directly On Resin Supports, Acc Chem Res 31 621-630 1998. 

Solid-phase chemistry is an efficient synthetic tool that, compared with solution-phase chemistry, simplifies the work-up of the reaction, allows the process to be driven to completion by using excess of reagents, and can be automatized [2a]. In recent years, many studies have been devoted to developing both surface-mediated and resin-supported synthesis. Today the solid-phase approach is not limited to peptides and oligonucleotides but is also used to synthesize molecules of lower molecular weight. 

The Jacobsen group has also shown that the recycling of the resin-bounded catalyst can be successfully performed [152,154]. Moreover, they have developed an efficient method for the hydrolysis of the aminonitrile into the corresponding amino acid. This method was apphed for the commercial production of optically active K-amino acids at Rhodia ChiRex (e.g. tert-leucine) the catalyst was immobihsed on a resin support (4 mol %, 10 cycles) and the intermediate hydrocyanation adduct was trapped by simply replacing TFAA with HCOOH/AC2O, for example. Highly crystalhne formamide derivatives were thus obtained in excellent yields (97-98% per cycle) with very high enantioselectivities (92-93% per cycle) [158]. 

Rhodium also has been reported as a catalyst for [2+2+2] alkyne cycloaddition in water. Uozumi et al. explored the use of an amphiphilic resin-supported rhodium-phosphine complex as catalyst (Eq. 4.60). The immobilized rhodium catalyst was effective for the [2+2+2] cycloaddition of internal alkynes in water,113 although the yields of products were not satisfactory. 

Numerous resin supports are commercially available for solid-phase synthesis and some allow the acquisition of quite reasonable quality spectra of compounds bonded to them - and some don t. The resins to avoid (if you intend trying to monitor your reactions by MAS-NMR) are any that are based purely on cross-linked polystyrene. These are too rigid and afford little or no mobility to any bound compound. These resins are relatively cheap and have high specific loadings but will give very poor spectra even in a MAS probe. We see little point in running spectra of compounds on these resins as the quality of the spectra make them virtually useless - and perhaps worse - potentially misleading. 

Many borohydrides are highly unstable and have to be used as freshly prepared ethereal solutions. However there are instances where the polymer-supported versions are more stable e. g. an Amberlyst anion exchange resin supported borohydride and cyanoborohydride [61], polyvinylpyridine supported zinc borohydride [62] and the corresponding zirconium borohydride [63]. Such compounds, in their labeled forms, should turn out to be very useful. 

Amphiphilic resin supported ruthenium(II) complexes similar to those displayed in structure 1 were employed as recyclable catalysts for dimethylformamide production from supercritical C02 itself [96]. Tertiary phosphines were attached to crosslinked polystyrene-poly(ethyleneglycol) graft copolymers (PS-PEG resin) with amino groups to form an immobilized chelating phosphine. In this case recycling was not particularly effective as catalytic activity declined with each subsequent cycle, probably due to oxidation of the phosphines and metal leaching. 

In another elegant approach (Scheme 18), a synthesis of 5-alkenyl-substituted 1,2,4-oxadiazoles relies upon a selenoxide. -elimination at the 5-a-carbon of the selenium resin-supported 1,2,4-oxadiazole 152. Access to compound 152 was achieved in two steps from the supported oxadiazole 150, which underwent deprotonation and alkylation at the 5-a-carbon to give the a-alkylated selenium resin 151. 1,3-Dipolar cycloaddition then gave the selenium resin-supported 1,2,4-oxadiazole 152 <2005JC0726>. 

Condensation of aromatic or aliphatic esters with resin-supported acetyl carboxylic acids 28 followed by cyclisation with hydroxylamine, activation of the linker, and cleavage using amines, provided highly substituted isoxazoles 30 and 31. This general method gave products in excellent yields and purities in which the regioisomers ratio can be easily controlled . 

Depending on the technical requirements such as corrosion resistance, pressure and temperature stability, industrial scale azo pigment synthesis is carried out in appropriate equipment. Suitable materials include cast iron, stainless steel, steel lined with rubber, acid-proof brick, enamel, synthetic resins supported by glass fiber, and wood. 

S Zalpsky, JL Chang, F Albericio, G Barany. Preparation and applications of polyethylene glycol-polystyrene graft resin supports for solid-phase peptide synthesis. Reactive Polymers 22, 243, 1994. 

The process has also been adapted using resin supported catalysts [e.g. 23-28]. Generally, the reactivity of the alkyl halides follows the normal pattern of I>Br>Cl, but secondary alkyl halides are less reactive and require high reaction temperatures and tertiary alkyl halides fail to react. 

Suspension Polymerized Particulate Resin Supports -Structural and Morphological Variants... 

Wang et al. investigated the catalytic behavior of cation exchange resin supported lanthanide(III) salts of the general structure (31) (Scheme 4.15), prepared from Dowex, Amberlite, Amberlyst and other resins [99]. It turned out that Am-berlyst XN-1010 and Amberlyst 15 complexed best with lanthanides(III). Thus, among others, electrophilic substitution of indole with hexanal and Mukayiama-type aldol reaction of benzaldehyde with ketene silyl acetal proceeded in excellent yields under catalytic conditions (Scheme 4.16). 

Other important examples of immobilized palladium catalysts (48)-(50) which were employed in Heck, Suzuki-Miyaura and allylic alkylation reactions are summarized in Fig. 4.4 [123]. Catalyst (49) is particularly noteworthy as it is a recyc-able amphiphilic resin-supported P,N-chelating Pd-complex which performs asymmetric allylic alkylations in water. 

The authors used this dendronized resin support (generation 1 and 2) (56) for the synthesis of 2-naphthalenesulfonamide (57) and N-phenylacetyl-L-phenylala-ninamide (58). Compound (57) was prepared via support-deprotection, coupling with 2-naphthalenesulfonylchlorid in the presence of DIPEA and subsequent... 

Uozumi, Y. Suzuka, T. pi-AUyhc sulfonylation in water with amphiphilic resin-supported paUadium-phosphine complexes. Synthesis 2008,1960-1964. 

Figure 18. Synthesis of the resin-supported indium Lewis acid catalyst 51.

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