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Abstract
Catalytic enantioselective acylation is a widely used method for the preparation of chiral compounds. A new class of nonenzymatic enantioselective acylation catalysts has been developed in our group. During the optimization and application of 2,3-dihydroimidazo[1,2-a]pyridine (DEEP) based catalysts, π-π and cation-π interactions between the acylated catalyst and the substrate were recognized to be vital to enantioselectivity and reactivity of acylation. Consequently, the second generation catalyst 7-chloro-2-pheny1-2,3-dihydroimidazo[1,2-a]quinoline (Cl-PIQ) was designed and synthesized to provide enhanced π interactions. Cl-PIQ exhibited high enantioselectivity in kinetic resolution of benzylic alcohols (s ≤ 117), cinnamyl alcohols (s ≤ 57) and 2-oxazolidinones (s ≤ 105), and it is one of the best catalysts in kinetic resolution of a variety of allylic alcohols. As an application of the methodology in natural product synthesis, (-)-lobeline was enantioselectively synthesized via desymmetrization by the catalysis of benzotetramisole (BTM), the third generation catalyst.
The structure-selectivity trends observed in catalytic asymmetric acylation shed light on the reaction mechanism, and directed the proposal of transition state models. On the other hand, the catalyst deactivation study revealed the complexity of the catalysis mechanism.