Polymer-supported reagents acylation

Weik and Rademann have described the use of phosphoranes as polymer-bound acylation equivalents [65]. The authors chose a norstatine isostere as a synthetic target and employed classical polymer-bound triphenylphosphine in their studies (Scheme 7.54). Initial alkylation of the polymer-supported reagent was achieved with bromoacetonitrile under microwave irradiation. Simple treatment with triethyl-amine transformed the polymer-bound phosphonium salt into the corresponding stable phosphorane, which could be efficiently coupled with various protected amino acids. In this acylation step, the exclusion of water was crucial. 

The use of polymer-supported reagents in combinatorial chemistry has received much attention in recent years, and a polymer-supported acylating reagent (supported on a ROMPGEL) has been used for the synthesis of 1,2,4-oxadiazoles in solution, (see Equation 37), <2000CCHT131>. 

An extended application of the resin-capture-release technique is depicted in Scheme 13. With the help of reagent 31, a functionalized pyridine was captured as an acyl pyridinium cation 32 on a solid support which was followed by Grignard addition and hydrolysis under acidic conditions to afford polymer-supported N-acylated dehydropyridinones 33 [39]. Advantageously, any unreacted acylium complex collapses to the parent resin upon workup. These heterocycles, which ideally can serve as scaffolds, are then released under basic conditions. 

Polymer-supported reagents and catalysts for acylation 89MI30. 

An acylated disaccharide 75 was efficiently prepared using polymer-supported reagents. Formation of glycosyl imidate 72 was carried out with Dowex 1-8X (OH form) as a polymer-supported base, and glycosylation of acceptor 73 with the imidate 72 was carried out using... 

Kinetic resolution with racemisation Enzymes versus whole organisms Desymmetrisation with lipases Immobilised enzymes in desymmetrisation Polymer-supported reagents and enzymes Effects of amines on lipases and esterases Other acylating enzymes Enzymatic Oxidation... 

Oscarson et al. [5] described the hydrolysis of compound 20 to 9 (89%) by treatment with KIO clay in methanol-water for 2 min under the action of microwave irradiation at 150 °C. Because polymer-supported reagents worked out well in acylation reactions, they also submitted 20 to microwave irradiation with polymer supported poly(4-vinylpyridinium-p-toluenesulfonate) (PPTS) in ethanol-water at 150 °C for 2 min and obtained 9 in 94% yield (Scheme 12.19). 

Solid-phase scavenger methods are employed with increasing frequency as a prehminary reaction cleanup step in combinatorial chemistry, and have recently become commercially available (Argonaut, Calbiochem-Novabiochem, Varian, Alltech). lilly researchers first reported on this approach, employing sohd supported electrophiles and nucleophiles for reaction purification in acylation and alkylation reactions. Yield and purity values reported were 90-95% and 50-99%, respectively, for a library generated by reductive amination. Parke-Davis researchers achieved the removal of known reaction product impurities by the application of custom synthesized polymer supported reagents, specifically polystyrene-divinylbenzene supported derivatives of methylisocyanate and tm(2-aminomethyl)amine for cleanup of by-products resulting from urea, thiourea,sulfonamide,amide, and pyrazole libraries. 

Alkyl and acyl thiocyanates and isothiocyanates are prepared in good yields from the corresponding halides by use of polymer-supported reagents, and a convenient approach to the synthesis of dialkylaminoalkyl isothiocyanates ... 

As mentioned before for other azolide reactions, acylations can be carried out with polymer-supported azolides as acylating reagents. For example, acetic acid hydrazide can be prepared with a polymer of l-acetyl-4-vinyl-imidazole/divinylbenzene (96 4) and hydrazine (no diacylation occurs when this method is used) [122]... 

Scheme 7.109 Amide synthesis utilizing a reusable polymer-supported acylation reagent.

This multi-step, one-pot process was taken further by integration of a third supported reagent for the sequential preparation of 3,5-diphenylpyrazole (Scheme 2.17). Following the previously established procedure, acetophenone was deprotonated and acylated to afford the 1,3-dicarbonyl species. This intermediate was easily separated from the spent polymers by filtration and passed without isolation into a suspension of the resin bound hydrazine salt (9), affording the desired pyrazole in 91% yield. In a subsequent publication, the authors reported that the depleted polymeric reagents from the first step of the conversion (i.e. (7) and (8)) were recovered and separated via a selective flotation procedure, enabhng them to... 

In 1982 Cardillo used a three-step sequence involving two supported reagent systems to convert /i-iodoamines into amino alcohols (Scheme 2.23) [45]. Polymer-supported acetate ions were used for the substitution of the iodide which immediately underwent acyl transfer to the amine. The resulting compound (10) was directly treated with hydrochloric acid to cleave the amide and the free base was subsequently obtained from the reaction by treatment with a resin-bound carbonate. This was of particularly synthetic value because of the high water solubiHty of these amino alcohol compounds that would have made aqueous work-up challenging. 

The selected example by Pop et al. [106] reported a polymer-supported 1-hydroxybenzotriazole derivative as a reagent for acylations of /V-nucleophiles in solution-phase combinatorial synthesis. The synthesis and the structure of the bound reagent are shown in Figure 7.13. 

FIGURE 7.13 Synthesis of polymer-supported 1-hydroxybenzotriazole derivative reagent for acylation of N-nucleophiles. 

Iminophosphoranes (117), (118) and their polymer-supported analogues (119), (120) (Scheme 24) have been found to catalyse the acylation of primary alcohols with enol esters with high yields and selectivities. Moreover, these ylide based catalysts appear more tolerant of sensitive functional groups than alternative Lewis base reagents. ... 

A somewhat different approach to a polymer-supported radical source was described by Giacomelli and coworkers, who used an N-hydroxythiazole 2(3)-thione anchored to a Wang resin [95]. The reagent was prepared in solution and equipped with a pendant COOH group to facilitate attachment to the resin. The applicability of the reagent in radical-mediated reactions was then investigated via a Hunsdiecker reaction (Scheme 6.24). Treatment of the reagent with an acyl... 

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