PEG resins

The same approach was readily adaptable to solid-phase synthesis. A small library of unnatural derivatives of 140 was prepared with variation of the configuration and nature of R1 and R4 and with substitution on the benzene ring <2000JC0186>. Three natural alkaloids, Verrucine A, B, and Anacine, were synthesized by a similar pathway and the pyrazino[2,l- ]quinazoline as opposed to the benzodiazepine structure of Anacine was proved <2001JNP1497>. Fiscalin B and other derivatives were prepared by solid-phase synthesis using polyethylene glycol (PEG) resin <2002USP6376667>. 

Combs and coworkers have presented a study on the solid-phase synthesis of oxa-zolidinone antimicrobials by microwave-mediated Suzuki coupling [38], A valuable oxazolidinone scaffold was coupled to Bal resin (PS-PEG resin with a 4-formyl-3,5-dimethoxyphenoxy linker) to afford the corresponding resin-bound secondary amine (Scheme 7.18). After subsequent acylation, the resulting intermediate was transformed to the corresponding biaryl compound by microwave-assisted Suzuki coupling. Cleavage with trifluoroacetic acid/dichloromethane yielded the desired target structures. 

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. 

Several reactions (3, 5, 11-14, and 16) were carried out on these resins under identical conditions to compare reaction rates on polystyrene and polystyrene-PEG resins.11 The results are collected in Table 7.1. These data show that reactions on polystyrene-PEG resin are not always faster than on polystyrene resins. For example, reaction 16 is much slower on polystyrene-PEG resin than on polystyrene resin. 

Another kind of solid support that has gained more popularity is the surface-modified polypropylene, such as the Multipin crown and Microtubes. Reaction 3 was carried out on lightly and highly cross-linked polystyrene resins (1 % and >20% divinylbenzene, respectively), poly sty rene-PEG resin, and a surface-functionalized Microtube reactor.12 The reaction kinetics on these supports is compared in Figures 7.4 and 7.5. The reaction on the highly cross-linked polystyrene resin was shown to be slower than on other supports and the reaction on Microtube was faster than on polystyrene resins. 

To assess the versatility of this reaction on solid support, several heterocyclic carboxylic acids were coupled to the PS-PEG resin (PAL linker). Applying the... 

PAL-PEG resin, Fmoc amino acids and coupling reagent N,N -diisopropylethylamine (DIPEA) and fhbcnzotriazolc-/V,/V,Ar,Ar-tetramct.hyl-uronium-hexafluoro-phosphate (HBTU) (Advanced ChemTech, Louisville, KY). 

The peptides can be synthesized automatically using Fmoc amino acids and PAL-PEG resin on a Milligen 9050 PepSynthesizer (17). 

Chen and Janda (288, 289) recently reported the use of non-cross-Unked polystyrene (NCPS) (290) as a soluble support with complementary solubility properties with respect to PEG resins. The synthesis of a complex prostaglandin structure 8.106 (291) using the chloromethyl NCPS support 8.102, the acid-labile THP linker, and the three synthons 8.103 (291), 8.104 (292), and 8.105 (293) is shown in Fig. 8.48. 

An amphiphilic polystyrene-poly(ethylene glycol) (PS-PEG) resin-support has been used successfully as a suitable support for asymmetric catalysts in aqueous media. A polymeric (R]-2-(diphenylphosphino) binaphthyl (MOP) ligand 205 anchored onto the PS-PEG resin was shown to be an effective chiral ligand for the enantioselective p-allyhc substitution under aqueous condihons (Scheme 3.67) [130]. 

Figure 6.1 Amphiphilic PS-PEG resin-supported palladium-phosphine complexes.

Figure 6.3 A library of PS-PEG resin-supported chiral phosphine ligands.

Thus, the reaction of the cycloheptenyl carbonate 29 with 5 equivalents of dibenzylamine in the presence of 8mol% palladium of the PS-PEG resin-supported 23-Pd complex was carried out in THF or dichloromethane and showed no catalytic activity at 25 °C, whereas the same system in water proceeded smoothly to give 91% yield of the cycloheptenylamine 41a (Scheme 6.4). 

Asymmetric aquacatalytic allylic Cj-subshtuhon was also achieved with nitromethane as a Cl nucleophile by using the PS-PEG resin-supported 23-Pd catalyst in which, under water-based conditions, nitromethane did not explode even under basic conditions (Scheme 6.6) [16]. To the best of the present author s knowledge. 

The PS-PEG resin-supported BINAP ligand was prepared and used successfully for the rhodium-catalyzed asymmehic 1,4-addihon reachon in water [29]. BINAP bearing a carboxyhc group at the 6-posihon was immobihzed by an amide bond on an amphiphihc PS-PEG NH2 resin (Scheme 6.7). The PS-PEG BINAP 59 was heated with Rh(acac)(G2H4)2 to form the PS-PEG-BlNAP-Rh complex. The polymeric BINAP-Rh complex showed high catalyhc achvity and high enanhoselectivity in water for the 1,4-addihon of phenylboronic acid to a,P-unsaturated ketones (Scheme 6.8). 

Several miscellaneous polymer-supported chiral phosphine ligands and oxazoline ligands are depicted in Figure 6.8 and Figure 6.9, respectively. Binaphthyl monophosphine MOP [36] was anchored onto PS-PEG resin at the 2 -, 6- and O -positions of its binaphthyl backbone (compounds 84, 85 and 86) [37]. The polymeric phos-... 

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