Solid-phase-supported domino reactions

multi-parallel synthesis lies at the forefront of organic and medicinal chemistry, and plays a major role in lead discovery and lead optimization programs in the pharmaceutical industry. The first solid-phase domino reactions were developed by Tietze and coworkers [6] using a domino Knoevenagel/hetero-Diels-Alder and a domino Knoevenagel/ene protocol. Reaction of solid-phase bound 1,3-dicarbonyl compounds such as 10-22 with aldehydes and enol ethers in the presence of piperidinium acetate led to the 1-oxa-1,3-butadiene 10-23, which underwent an intermolecular hetero-Diels-Alder reaction with the enol ethers to give the resin-bound products 10-24. Solvolysis with NaOMe afforded the desired dihydro-pyranes, 10-25 with over 90 % purity. Ene reactions have also been performed in a similar manner [7]. 

A combination of a multicomponent Ugi transformation and an intramolecular Diels-Alder reaction has been developed by Paulvannan [13]. Hence, condensation of the resin-bound (acid-labile ArgoGel-Rink resin) amine 10-37 with a tenfold 

Amine building blocks Fumaric acid building blocks 

Recently, Oikawa and coworkers also published a successful parallel synthesis using a domino Ugi/Diels-Alder process [14]. Thus, reaction of immobilized fur- 

In this context it must be mentioned that the procedure by Kennedy and coworkers, in which a novel resin-bound isonitrile is applied in an Ugi multicomponent reaction for the synthesis of 2,5-diketopiperazines and 1,4-benzodiazepine-2,5-diones, was discussed earlier, in Chapter 9. 

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Over the past 5 years we have studied high-pressure multicomponent domino cycloaddition reactions in the liquid phase and on solid supports. Multicomponent domino cycloaddition reactions can generate mono-, di- and tricyclic systems in an efficient manner depending on the reaction components used. Application of high pressure is sometimes essential for the progress of every individual step of a... 

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