Michael iminium-enamine approach

Jprgensen and coworkers exploited an approach in 2005 by designing a three-component reaction involving iminium/enamine activation (Scheme 2.23). They demonstrated that thiols 84 can initiate the sequence by a thia-Michael addition to... 

The mechanism proposed for the transformations is illustrated in Scheme 1.77. The P-keto ester 176 approaches the planar iminium ion from the Re-f cQ due to steric hindrance of the bulky substituents at the chiral substituent in the pyrrolidine ring of catalyst 128. Hydrolysis of the enamine intermediate leads to the formation of Michael adducts 178 in a 1 1 diastereomeric mixture. The role of AcONa is therefore to promote the aldol reaction and the consequent consumption of the optically active product 179. Finally, the stronger base (K COj) deprotonates the alcohol and enables the intramolecular Sj 2 reaction, which leads to one-pot formation of the highly functionalized products 177. 

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