Organocatalyzed Cascade and Multicomponent Reactions

Because of these numerous reports, only selected examples are provided in this section. Most of them deal with double cascade reactions, mainly centered on Michael-type reactions. However, a few remarkable reports involving triple and quadruple cascade reactions are also presented. 

1 Double Cascade Reactions Amine-based organocatalysis are often employed for these cascade reactions because they can present a dual-activation mode depending the system involved, via enamine or iminium catalysis. 

General Procedure for One-Pot Diels-Alder/Benzoin Condensation A vial equipped with a Teflon-coated stir bar and a plastic screw cap was charged with (f )-2-(diphenyl((trimethylsilyl)oxy)methyl)pyrrolidine (0.02 mmol, 6.5 mg, 20 mol%). Then, 2,4,6-trimethylbenzoic acid (TMBA, 0.02 mmol, 3.2 mg, 20mol%) and toluene (0.2 mL) were added in one portion, and the resulting solution was stirred at ambient temperature for 10 min to allow the catalyst salt formation. The reaction was started by the sequential addition of the aldehyde (0.12 mmol, 1.2 equiv) and dibenzoylethylene (0.1 mmol). The vial was sealed and kept in a water bath (ther-mostated at 40 °C). After 48 h, the vial was removed from the water bath and cooled to room temperature. Then, 0.3 mL of toluene, sodium acetate (0.2 mmol, 16.4 mg. 

2 equiv), and 6,7-dihydro-2-pentafluorophenyl-5//-pyrrolo[2,l-c]-l,2,4-triazolium tetrafluoroborate (0.02 mmol, 7.2 mg, 20mol%) were added sequentially, and the resulting solution was stirred at 50 °C for 40 h. The reaction was cooled down to ambient temperature and quenched with an aqueous solution of sodium bicarbonate (0.2 mmol, 16.8 mg, 2 equiv in 1 mL of water). The mixture was stirred for 30 min, and the crude product was extracted three times with ethyl acetate. The organic phase was dried with anhydrous sodium sulfate, filtered, and the solvent was removed under vacuum. The product was isolated by flash column chromatography. 

2 Triple Cascade Reactions Such cascades involve the formation of at least three novel bonds, and, to be efficient, this type of tandem reactions needs judicious choice of substrates and catalysts. 

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