Cycloaddition Reactions on a Polymeric Support

Most common are carbene additions, [2 -1- 2]-cycloadditions, [2 -1- 3] heterodipolar cycoladditions [238], and [2 -1- 4]-cycloadditions that comprise Diels-Alder and hetero-Diels-Alder (HDA) reactions [239]. Apart from these, there are also a number of tandem cyclization or condensation reactions that are formal cycloadditions. 

In many cases the choice of support-bound fragment determines which and how functional groups, being structural diversity elements, can be introduced. For this reason we would like to focus on some synthetic methods which provide the support-bound building blocks for subsequent cycloaddition reactions. 

Generally, the electrocyclic cycloaddition reactions are performed thermally, without catalysis. Diels-Alder reactions are further facilitated by high pressure in hydrophobic structures, suffering hydrophobic collapse within an aqueous environment. Photochemical cycloadditions are often limited by the penetration of the polymeric support by the light of the desired wavelength. However, especially in case of hetero Diels-Alder reactions, Lewis acid catalysis has been applied. On a solid support the use of acid catalysis is often limited by the stability of the support linker, since most common linkers have been designed to be cleavable under acidic conditions. Table 4 shows some of the Lewis acids and the support link used. 

Hetero-Diels-Alder with inverse electron demand Wang ester Euffodjs a,P-unsaturated carbonyl [240] 

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Samanta et al. [23] conveniently synthesized the 1,5-disubstituted imidazoles (xxv) on a polymeric support using base-promoted 1,3-dipolar cycloaddition reaction of p-toluenesulfonylmethyl isocyanide (TOSMIC) with immobilized imines under microwave irradiation. 

Uncatalyzed Diels-Alder reactions and [2 + 3]-heterodipolar cycloadditions can be performed on a variety of acrylic or maleimide-based resins. One simple method is to link an acrylic residue to a polymeric support via an ester or an amide linkage. 

Resin-bound diazoimides 190 were subsequently reacted with different electron deficient acetylenes 191 in benzene at 80°C for 2 hours in the presence of Rh2(OAc)4 as a catalyst. Analysis of the crude products showed exclusively the presence of the desired furans 192 and excess unreacted acetylene, which, when sufficiently volatile (e.g propiolate esters), were eliminated in vacuo to provide furans of high purity. To avoid contamination of the desired furan product with residual, non-volatile acetylene, a two step sequence was implemented for the cycloaddition reaction. Thus, C-labelled diazoimide 193 was allowed to react with a large excess (10 eq) of dimethyl acetylenedicarboxylate (DMAD) 194 in the presence of Rhj(OAc)4 at room temperature in anticipation of trapping the bicyclic intermediate 196 on the polymeric support. After washing the... 

Recently, Kerr introduced a promoter anchored to a solid support to facilitate workup after the reaction. For example, the PKR proceeds to completion by use of the amine A-oxide anchored on solid support 14, and then the polymeric amine is recovered by simple filtration. The recovered polymer is cleaned by washing with a THF-aqueous 2 M HGl mixture (2 1 mixture), followed by washing of hydrochloride salt with a 10% solution of Pr2NEt in DMF. The resultant resin is oxidized again and then used without loss of activities.Kerr and Pauson also successfully employed sulfide promoters anchored on the solid support 15 for this cycloaddition (Figure 1). ... 

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