Polymer-bound aryl iodides

The suitability of the polymer-Hnker conjugate was examined for a variety of transformations, in particular Pd°-catalyzed reactions. For instance, the polymer-bound aryl iodide (63) was transformed quantitatively in a Heck reaction to a cinnamic acid ester (64) and to biphenyl (66) in a Suzuki reaction. It gave an alkyne (65) in a Sonogashira reaction (Scheme 10.12). 

The copper-catalyzed coupling of polymer-bound aryl iodides with stannanes has also been demonstrated.64... 

Another resin-capture approach has been pubhshed in relation to the synthesis of tetrasubstituted ethylenes via Suzuki coupling reactions (Scheme 20) [42, 53]. A 25-member hbrary was synthesized using five alkynes, five aryl halides, and a polymer-bound aryl iodide. The alkynes 55 were converted into bis(boryl)alkenes 56 in solution, and the crude intermediates were used in Suzuki reactions with an excess of aryl halide. When all of the bis(boryl)alkene 56 had been consumed, the aryl iodide resin 59 was added to the reaction mixture and the reaction continued on the solid support. Side products such as 58, arising from a double Suzuki reaction, remained in solution and could be washed away. Compounds 60 were cleaved from the polymer using trifluoroacetic acid and products 61 were obtained in > 90% purity. 

Both polymer-bound aryl halide and polymer-bound boronic acid give satisfactory results. Maximal diversity is obtained by in situ hydro-boration of polymer-bound aryl iodides followed by addition of aryl iodides. 

The benzylzinc bromide 63 reacted preferentially with the polymer-bound aryl iodide 62, without attacking the triflate. Then the benzylzinc bromide 64 was add to the reaction mixture, and coupling with the triflate occurred to afford 65 after cleaving from the polymer [64],... 

Finally, Fukase and coworkers have used the Sonogashira reaction to anchor glycoside moieties with a pendant acetylenic side chain to polymer-bound aryl iodides, forming a novel alkyne linker system [100]. 

A divergent protocol for a solid-phase synthesis of 3-substituted 2,5-biarylfurans was reported. Thus, reaction of furan zincate A with polymer bound aryl bromide or iodide provides resin intermediates 61. Subsequent bromination-Suzuki coupling reaction followed by further transformations gives rise to structurally diverse 2,3,5-trisubstituted furans 68 in good overall yields and chemical purities <00TL5447>. 

Alternatively, boranes can be prepared in solution and then coupled with support-bound carbon electrophiles. The Suzuki coupling of alkylboranes, generated in situ from 9-BBN and alkenes, with brominated cross-linked polystyrene has been used to link substituted alkyl chains directly to the polymer (Entry 4, Table 5.3). Alkylboranes have also been used to alkylate polystyrene-bound aryl iodides (Entries 3 and 5, Table 5.3). 

Buchwald has shown that, in combination with palladium(II) acetate or Pd2(dba)3 [tris(dibenzylideneacetone)dipalladium], the Merrifield resin-bound electron-rich dialkylphosphinobiphenyl ligand (45) (Scheme 4.29) forms the active polymer-supported catalysts for amination and Suzuki reactions [121]. Inactivated aryl iodides, bromides, or even chlorides can be employed as substrates in these reactions. The catalyst derived from ligand (45) and a palladium source can be recycled for both amination and Suzuki reactions without addition of palladium. 

To a heavy-walled flask equipped with a nitrogen inlet side arm was added resin-bound terminal acetylene (684.4 mg resin, 0.274 mmol, 0.448 mequiv/g resin) and aryl iodide (120.6 mg, 0.3011 mmol) (Scheme 11). The flask was evacuated and back-filled with nitrogen a minimum of three times. The supernatant of a separate 0.2 M catalyst cocktail solution (previously prepared) was added via cannula (5 mL, 3.0 mmol) to the reaction flask. The flask was kept sealed at 65°C for 12 h and agitated periodically to remix polymer beads stuck on flask walls. The beads were then transferred to a fritted filter using methylene chloride and washed with methylene chloride (21 mL). Excess aryl iodide can be recovered from the first methylene chloride wash. All further washes were carried out in the ratio of 30 mL/g resin. The resin was washed sequentially with DMF, 0.05 M solution of sodium diethyl dithiocarbamate in 99 1 DMF-diisopropylethylamine,... 

Boronates have been used in a variety of linker types either as linkers for diols [42] or as precursors for metal-mediated cleavage. A boronic acid ester, which contains an aryl iodide moiety attached by an appropriate tether, can act as an intramolecular arylation agent. A polymer-bound precursor furnished a macrocydic constrained / -tum peptide mimic via biaryl coupling, leading to cleavage [43] (Scheme 6.1.10). 

Phosphonates have also been prepared from alcohols and (Ar0)2P(=0)Cl, NEts and a TiCl4 catalyst. ° The reaction of (R0)2P(=0)H and aryl iodides with a Cul catalyst leads to aryl phosphonates. " Polymer-bound phosphonate esters have been used for olefination. Dienes are produced when allylic phosphonate esters react with aldehydes. 

Polymer-bound ligands Aryl iodides Recyclable, increased stability [115]... 

The inverse temperature-dependent solubility in aqueous media of polymer-bound palladium(0)-phosphine catalysts, based on the water-soluble polymer poly(Wisopropyl)acrylamide (PNIPAM) 28, was also used to recycle and reuse these catalysts in nucleophilic allylic substitutions (Equation (8)) and cross-coupling reactions between aryl iodides and terminal alkynes (Equation (9)). The catalyst was highly active in both reactions, and it was recycled 10 times with an average yield of 93% in the allylic nucleophilic substitution by precipitation with hexane. ... 

Terminally functionalized PIB oligomers have been used in a thermomor-phic heptane/JV,N-dimethylacetamide mixture as supports for thermally stable SCS-Pd(II) Heck catalyst precursors. A PIB-supported SCS-Pd(II) Heck catalyst was prepared from the carboxyl-terminated PIB oligomer by the sequence of reactions shown in Eq. 61. The PIB-bound SCS-Pd(II) species 125 so ormed was then used to carry out Heck chemistry (Eq. 62). As was true for SCS-Pd(II) species on other polymers [154,155,162], this catalyst was only effective for aryl iodides or activated aryl bromides. However, the catalyst could be used through... 

Various aryl bromides and iodides are suitable for this reaction. The reaction conditions may include microwave irradiation (Table 7, entry 6). It is interesting to note that a Stille coupling can be performed on a polymer-bound halobenzyl ester, which subsequently was cleaved by Pd-catalyzed hydrogenation to give the corresponding substituted methylarenes in the liquid phase (Table 7, entry 8). 

Aryl-alkenyl and aryl-aryl cydizations via Stille coupling are far less developed. In the case of alkenyl-aryl couplings, the olefmic moiety can be extracyclic or intracyclic with Z or E stereochemistry. An example is the cyclization of polymer-bound alkenylstannane with aryl iodide moiety in the total synthesis of (S)-zeara-lenone [127] (Scheme 6.16). 

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