Three component coupling reaction chiral phosphoric acid

Hu et al. developed a system that involved cooperative catalysis by a chiral phosphoric acid and an achiral rhodium complex (Scheme 3.37) [81]. They applied the binary catalytic system to a three component coupling reaction among a diazoesters, primary alcohols, and aldimines. The steric bulkiness of the primary alcohol had a significant effect on both diastereo and enantioselectivities. The sterically demanding 9 anthracenemethanol was the best component to give p amino a alkoxy esters with excellent stereoselectivities under the combined and cooperative catalysis by phosphoric acid ll and the rhodium complex. 

Scheme 3.37 Chiral phosphoric acid and rhodium complex binary catalytic system for three component coupling reaction.

The synthesis of (-l-)-monomorine I (1562), by Schneider and coworkers used an asymmetric three-component Mannich coupling between the vinylketene acetal 1635, p-anisidine (1636), and ethyl 4-oxobutanoate (1637) in the presence of the chiral phosphoric acid 1638 as catalyst to furnish the (il)-pyrrolidin-2-one (+)-1639 in 80% yield and 99% ee within 10 min at —55 °C (Scheme 207). ° The stmcture of the product was confirmed by X-ray crystallography. This reaction could be performed on a 32 mM scale by increasing the time to 16 h with little loss of... 

Urea and its derivatives can form imines when treated with aldehydes. In the presence of [3-ketoesters, these imines are subject to nucleophilic attack followed by intramolecular imine formation. This three-component transformation is known as the Biginelli reaction [94]. The resulting products are dihydropyrimidi-nones, which are compounds of high importance in medicinal chemistry [95]. In 2006, Gong and coworkers reported the first organocatalytic Biginelli reactions. Several different aromatic aldehydes 186, ]3-ketoesters 188, and (thio)urea (187) were successfully coupled in the presence of chiral phosphoric acid catalyst 99a (Scheme 42.43). Whereas aromatic aldehydes delivered the desired Biginelli... 

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