Multicomponent MBFTs for BRMs

In the preceding section, we already touched upon reactions that involve more than two input substrates. MCR cascades, however, often do not require organocatalysis for activation or selectivity. The desired selectivity frequently originates from the chirality of one of the inputs, such as chiral imines, aldehydes, or amines [23]. By exploiting this feature, many distinct MCRs have been applied in the synthesis of BRMs and are currently exploited for commercial use [24]. 

The supremacy of MCRs is illustrated by excellent atom economy, step efficiency, and mild reaction conditions. Many of the MCRs utilize the reactivity of imines by in situ condensation of (chiral) amines on carbonyls. Furthermore, frequent use of unconventional isocyanide groups, in, for example, the Ugi MCR, is characteristic. More interesting features of the MCR strategy will be addressed in further detail in due course. 

Dissection of the reaction sequence results in a tandem Knoevenagel condensation/A-carbamoyl-Mannich/condensation reaction sequence, which was first exploited by Biginelli in 1891. The resulting dihydropyrimidone scaffold is represented in many medicinal products, which are now produced by this efficient. 

Like many other MCRs, the Hantzsch protocol usually commences with a condensation reaction that produces an imine from the amine and aldehyde. In this case, however, the Knoevenagel adduct undergoes addition by the nucleophilic p-keto ester, which generates the intermediary dihydropyranol. Ammonium acetate addition then finally initiates the expected cyclocondensation to give the aminal. Although the 

The product (112) of D-xylose, allyl amine, and styrylboronic acid was then subjected to a protection/metathesis/dihydroxylation/deprotection/cyclization sequence that produced stereoisomerically pure (-F)-uniflorine A over a total of 11 steps. 

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