Resin Capture

As shown above, the second PASP strategy to purify a crude reaction mixture after the synthesis is to separate the desired product by selective covalent derivatization with a fuctional-ized resin and subsequent filtration and rinsing. After formation of the product in solution, it reacts selectively with a solid support while impurities and unreacted substrate remain in solution and are washed away. This resin capture concept [39] has been introduced using the Ugi four-component condensation to prove this purification approach. After the condensation, the reactivity of the enamide allowed the specific reaction with Wang resin under anhydrous acidic conditions. The resin was then washed with methanol and dichloromethane, and the subsequent cleavage performed with trifluoroacetic acid in dichloromethane. The final carboxylic acids were characterized without further purification and were >95 % pure.

Another resin capture approach has been published in the synthesis of tetrasubstituted ethylenes via Suzuki coupling reactions [40,41] (Scheme 21). A 25-member library 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 was con sumed, the aryl iodide resin 59 was added to the reaction mixture and the reaction continued on solid support. Side reactions such as a double Suzuki reaction gave products 58 that remained in solution and were washed away. The compounds 60 were cleaved from the polymer using trifluoroacetic acid, and the products 61 obtained in >90 % purity.

The resin capture approach combines the ease of solution synthesis with the ease of solid-supported isolation and purification, but the unreacted starting materials and possible side products have to be inert to the capture.

Procedure: Preparation of 61 [40]

A small test tube was charged with 56 (10 equiv.), organohalide (15 equiv.), Pd(PPh3)2CI2 (0.3 equiv.), 3 M KOH (20 equiv.) and sufficient dimethoxyethane to bring the concentration of 56 to 0.5 M.The test tube was covered with a septum, flushed with N2 and heated overnight. Another test tube was charged with 100 equiv. of KOH and 1 equiv. of 59 and flushed with N2.The dimethoxyethane/KOH solution was syringed into the tube containing the polymer and heated overnight. The polymer was filtered from of the solution and washed successively with water, methanol, ethyl acetate and dichloromethane.The solid-bound products 60 were cleaved from the polymer with 30 %TFA in dichloromethane, to give 61.

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