Polymers, 1,3-dipolar cycloaddition reactions

R. J. Pieters, D. T. S. Rijkers, and R. M. J. Liskamp, Application of the 1,3-dipolar cycloaddition reaction in chemical biology Approaches toward multivalent carbohydrates and peptides and peptide-based polymers, QSAR Comb. Sci., 26 (2007) 1181-1190. 

Dipolar cycloaddition reactions are of main interest in nitrile oxide chemistry. Recently, reviews and chapters in monographs appeared, which are devoted to individual aspects of these reactions. First of all, problems of asymmetric reactions of nitrile oxides (130, 131), including particular aspects, such as asymmetric metal-catalyzed 1,3-dipolar cycloaddition reactions (132, 133), development of new asymmetric reactions utilizing tartaric acid esters as chiral auxiliaries (134), and stereoselective intramolecular 1,3-dipolar cycloadditions (135) should be mentioned. Other problems considered are polymer-supported 1,3-dipolar cycloaddition reactions, important, in particular, for combinatorial chemistry... 

The 1,3-dipolar cycloaddition of nitrones to vinyl ethers is accelerated by Ti(IV) species. The efficiency of the catalyst depends on its complexation capacity. The use of Ti( PrO)2Cl2 favors the formation of trans cycloadducts, presumably, via an endo bidentate complex, in which the metal atom is simultaneously coordinated to the vinyl ether and to the cyclic nitrone or to the Z-isomer of the acyclic nitrones (800a). Highly diastereo- and enantioselective 1,3-dipolar cycloaddition reactions of nitrones with alkenes, catalyzed by chiral polybi-naphtyl Lewis acids, have been developed. Isoxazolidines with up to 99% ee were obtained. The chiral polymer ligand influences the stereoselectivity to the same extent as its monomeric version, but has the advantage of easy recovery and reuse (800b). 

SCS-MP2 and the new perturbative B2-PLYP density functional methods provide accurate reaction barriers and outperform MP2 and B3-LYP methods when applied to the 1,3-dipolar cycloaddition reactions of ethylene and acetylene.39 Phosphepine has been shown to catalyse the asymmetric 3 + 2-cycloaddition of allenes with a variety of enones (e.g. chalcones) to produce highly functionalized cyclopentenes with good enantiomeric excess.40 The AuPPh3SbF6 complex catalysed the intramolecular 3 + 2- cycloaddition of unactivated arenyne- (or enyne)-yne functionalities under ambient conditions.41 A review of the use of Rh(I)-catalysed 3 + 2-cycloadditions of diaryl-and arylalkyl-cyclopropenones and aryl-, heteroaryl-, and dialkyl-substituted alkynes to synthesise cyclopentadienones for use in the synthesis of natural products, polymers, dendrimers, and antigen-presenting scaffolds has been presented.42... 

In all instances only starting material was isolated with the and C-NMR confirming the absence of any triazole signals. This clearly illustrates that the dipolar cycloaddition reaction only takes place in the presence of cucurbituril, which has a dual function to catalyze the cycloaddition reaction and in the process become inextricably threaded onto the polymer chain. The sequence of events involved in this catalytic self-threading process is presented in Fig. 1.45. The combination of using monomers with bulky in-chain stopper groups and the catalyst self-threading onto the polymer backbone limits this catalysis to a turnover of exactly 1. 

In the last few years, click reactions, as termed by Sharpless et al. [280] received attention due to their high specificity, quantitative yields, and good fidelity in the presence of most functional groups. The click chemistry reaction includes a copper-catalyzed Huisgen dipolar cycloaddition reaction between an azide and an alkyne leading to 1,2,3-triazole. Recent publications on this click reaction indicate that it is a useful method for preparation of functional polymers [281]. 

Theoretical studies suggest that the cycloaddition of nitrones, to C6o and CNTs, is the least favored reaction of the several 1,3-dipolar cycloaddition reactions studied (03JA10459, 09CEJ13219). Despite these premises, the experimental results show that it is possible to functionalize MWCNTs with cyclic nitrones (09CC252,1 ICMl923). While fullerene and SWCNTs do not apparently react with nitrones, MWCNTs react with cyclic nitrones upon refluxing in DMF. The harsh reaction conditions require the use of stable nitrone 74. This reaction produces functionalized CNTs 75 that are pretty soluble in DMF and dispersible in polymers. The markedly different reactivity of MWCNTs with respect to SWCNTs arises from the higher numbers of defects that are present on the wall of MWCNTs. A Raman measurement and a theoretical study support the hypothesis. 

Hecht and co-workers developed another class of polymers based on allgme-azide click chemistry. The synthesis of these new polymers was an A2-I-B2 step-growth polymerization, with A2 corresponding to the 2,6-diethynylpyridine monomer and B2 to the 3,5-diazidohenzoate monomer that reacted together under Cu-catalyzed 1,3-dipolar cycloaddition reaction conditions (Figure 5.22). 

M. Moore, P. Norris, Dipolar cycloaddition reactions on a soluble polymer-supported dipolar-ophile synthesis of sugar-derived triazoles. Tetrahedron Lett. 1998, 39, 7027-7030. 

S. Kobayashi, R. Akiyama, Lanthanide triflate-catalyzed 1,3-dipolar cycloaddition reactions of polymer-supported nitrones with alkenes for the preparation of diverse 2-isoxazoline derivatives. Tetrahedron Lett. 1998, 39, 9211 9214. 

The use of AB2 monomers containing an internal triple bond as A-unit and two azides as B-units for the synthesis of hyperbranched polymers was developed by the same group (Figure 8.7) (Scheel et al., 2004). Hyperbranched polymers containing a mixture of 1,4- and 1,5-substituted triazoles were obtained, as the internal alkynes can only react via the classical thermal induced 1,3-dipolar cycloaddition reaction. However, it was possible to synthesize fully soluble products by low-temperature (45 °C) autopolymerization in bulk. The end product contains a large number of reactive azide functionalities that can be further postfunctionalized by CuAAC reaction with the desired alkyne-containing compound. 

The polymer-stabilized monovalent copper Cu(l)—poly(2-aminobenzoic acid) shows a high catalytic activity toward azide—alkyne 1,3-dipolar cycloaddition reactions carried out at room temperature, in the presence of water as a solvent. Under aerated conditions, catalytic efficiency was proved for at least five cycles [40]. Cu(OAc)2 immobilized on a polystyrene-anchored imidazole... 

A strategy involving sequential 1,3-dipolar cycloadditions has been reported for the synthesis of novel bis-isoxazolo substituted piperidines 192a and 192b (Eqs. 18 and 19) [53]. It consists of the Michael addition of an unsaturated alkox-ide 185 to )3-nitrostyrene 184 followed by an INOC or ISOC reaction to provide isoxazolines 187-189 (Eq. 18 and Table 18). A polymer supported acyl chloride... 

Poly(ethylene glycol) supported liquid-phase syntheses by both the reaction of (polyethylene glycol (PEG))-supported imines with nitrile oxides, generated in situ from aldoximes, (300) and 1,3-dipolar cycloadditions of nitrile oxide, generated in situ on soluble polymers with a variety of imines (301, 302) have been described. The solid-phase synthesis of 1,2,4-oxadiazolines via cycloaddition of nitrile oxide generated in situ on solid support with imines has also been elaborated (303). These syntheses of 1,2,4-oxadiazolines provide a library of 1,2,4-oxadiazolines in good yields and purity. 

The ability of nitrile oxides to undergo addition and cycloaddition reactions makes it possible to use them in polymer chemistry and technology. Major trends might be synthesis, modification, cross-linking of polymers, addition of nucleophiles, and 1,3-dipolar cycloaddition of nitrile oxides. Taking into account the scarcity of reviews devoted to this topic, not only recent but also previous references will be cited in this subsection. 

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