Proline Derivatives and MacMillans Catalyst

Efficient L-proline-catalyzed Robinson annulation was reported in the early 1970s by two separate groups in industry one at Schering in Germany [27] and the other at 

Hoffman-La Roche in the USA [28]. The so-called Hajos-Parrish-Eder-Sauer-Wiechert reaction provided access to key intermediates for the synthesis of natural products and offered a practical route to the Wieland-Miescher ketone (Equation 10.12). 

Subsequently, MacMillan reported the second-generation MacMillan s catalyst Sb for the Friedel-Crafts alkylation reaction of pyrrole to, form a,p-unsaturated aldehydes (Equation 10.15) [32]. 

Following the seminal work on proline-catalyzed reactions, a range of proline- and proline derivative-catalyzed asymmetric reactions, including the Mannich reaction, Michael reaction, a-functionalization of carbonyl compounds, and cycloaddition reactions, have been developed [33]. 

Recently, two Japanese groups independently synthesized the anti-influenza ncuramidasc inhibitor (—)-oseltamivir by using a chiral organocatalyst in the key reactions. 

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