Polystyrene support, subsequent

To address the purification issue, which frequently is a bottle-neck in the fast microwave chemistry, a solid-phase catch and release methodology was utilized in a two-component, two-step synthesis of l-alkyl-4-imidazolecarboxylates [45]. In the first step, a collection of isonitriles 25 was immobilized onto a solid support by the reaction with the commercially available N-mclhyl aminomethylated polystyrene 26. Subsequent treatment with various amines brought about simultaneous derivatization and release of the desired imidazoles 27 back into solution. Significantly, only derivatized material was released from the resin, thus ensuring high purity of the desired product. Both steps of the reaction were substantially accelerated by microwave dielectric heating, resulting in the overall reaction time reduction from 60 hours to 70 minutes (Scheme 18). 

In some palladium-catalyzed cyclizations of enynes a [2 + 2] cycloaddition with subsequent metathesis-like rearrangement leads to other cyclic products50,51. The transition metal catalyzed Alder ene type cyclization reactions can also be applied to diynes52 and to enal-lenes53-55. The latter reaction is best performed using a polystyrene-supported nickel(II)/ chromium(II) catalyst. With the appropriate choice of substituents complete stereoselectivity can be achieved using this method55. 

In more recent work a different polystyrene supported dehydrating agent (Fig. 16.4a) was used for synthesis of 1,3,4-oxadiazoles under thermal and microwave conditions [107]. Addition of a homogeneous base, for example guanidine, improved the cyclodehydration reaction and led to completion under thermal and, even more significantly, microwave conditions. This required subsequent purification steps to remove the base for clean and quantitative isolation of the desired products, however. On the other hand, use of a polymer supported phosphazene base (Fig. 16.4b) as a base additive circumvents the need for additional purification of the reaction mixture for product isolation. 

Shuttleworth and Ailin reported the use of polystyrene-supported oxazolidinone 60 for the synthesis of chiral carboxylic acids 61 (Scheme 3.5.3). Preparation of 60 was accomplished in five steps. Acylation, enolate alkylation and subsequent hydrolysis afforded carboxylic acid 61 in 42% yield and with an enantiomeric excess of 96%. The chiral auxiliary 60 was recovered and could be re-used. 

Several variants of polystyrene-supported [bis(acyloxy)iodo]arenes have been developed [11-21]. Poly[(diacetoxyiodo)styrene] (4) can be prepared in two steps from commercial polystyrene 1 with an average molecular weight ranging from 45 000 to 250 000 [11-13,19-21]. In the first step, polystyrene 1 is iodinated with iodine and iodine pentoxide in sulfuric acid to givepoly(iodostyrene) 3, which is subsequently converted into the diacetate 4 by treatment with peracetic acid (Scheme 5.3) [11, 13]. The loading capacity of the polymeric reagent 4 obtained by this procedure (Scheme 5.3) varies from 2.96 to 3.5 mmol g as measured by iodometry and elemental analysis [11-13]. 

Subsequently, we and Toy et al. found that insoluble polystyrene-supported triphenylphosphine is an effective catalyst for the reactions between vV-tosyli-mines and methyl vinyl ketone. The corresponding aza-MBH adducts were obtained in excellent yields and the catalysts could be reused.Subsequently, the non-phosphane-bearing styrene aromatic rings have been functionalized with polar groups and a series of such catalysts were examined for their... 

Nevertheless, such reactive functions from pre-stages on a modified support may interfere later on with steps of the Merrifield peptide synthesis causing unforeseen troubles. From this shortly depicted complex of problems of subsequent modification of polystyrene supports, the following consequences may be deduced ... 

Cyclopentadienylrhodium complexes were used for tandem Claisen re-arrangement-hydrocylation of the allylenolethers 62 to the pentenals 63, which were subsequently cyclized to the cyclopentanones 64 (Scheme 26). Activity of the monomeric (rj -C5H5)Rh(CO)2 65 and the polystyrene supported catalyst 66 was compared. The results clearly showed that the latter one gave the better results (Table 13) [33]. 

It has to be noted that the temperatures up to 220 °C involved in the transformations on polystyrene-based support do not affect the resin stabihty. The controlled microwave irradiation appeared to be very effective in speeding up the linking of 2(lH)-pyrazinones to an appropriate resin as well as in accelerating the rate of subsequent solid-phase Diels-Alder reaction and the following cleavage of a resulting pyridinone from the sohd support. 

In a recent study, another method for microwave-assisted heterocycle synthesis leading to a small set of imidazole derivatives has been reported [54], These pharmaceutically important scaffolds were synthesized utilizing polymer-bound 3-N,N-(dimethylamino)isocyanoacrylate. This polymer support was easily prepared by treatment of [4-(bromomethyl)phenoxy]methyl polystyrene with a twofold excess of the appropriate isocyanoacrylate potassium salt in N,N-dimethylformamide (Scheme 7.37). The obtained intermediate was subsequently treated with N,N-di-methylformamide diethyl acetal (DMFDEA) in a mixture of tetrahydrofuran and ethanol to generate the desired polymer-bound substrate. 

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. 

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