engleski

Enantioselective Organocatalytic Construction of a Congested Tetrasubstituted Stereogenic Center on Pyrrole β-(C3)-Position

Stereoselective functionalization of pyrroles is a challenging task. Because of their inherent small molecular size, the coordination of pyrroles with chiral catalysts results in weak steric interactions, which leads to difficulties in controlling the enantioselectivity. Reactions on pyrroles predominantly occur at its more nucleophilic α-(C2)-position. On the other hand, stereoselective functionalization β-(C3)-position of pyrrole is usually more difficult to achieve. β-Functionalized pyrroles serve structural cores of many biologically active compounds such as Prodigiosin and Rhazinilam. Only two systematic studies are reported for the construction of a tetrasubstituted stereogenic center on pyrrole β- (C3) position, and both rely on usage of chiral transition-metal complexes. However, in the contrast to these elegant examples, there are no reports in literature for the preparation of such compounds in an organocatalytic fashion. Herein, we report an enantioselective C-H functionalization of pyrroles for the construction of a tetrasubstituted stereogenic center on C3 position mediated by chiral phosphoric acid (CPA). Key to the success of this transformation is the in situ generation of the reactive ketiminium species from 3-hydroxyisoindolinones. The transformation proceeds rapidly with a broad range of ketimines and 2, 5-disubstituted and 2- monosubstituted pyrroles to afford products in up to 96% yield, and up to 98, 5:1, 5 e.r. The mechanism of stereochemical induction is investigated, and the reaction is successfully conducted on a larger scale.

stereoselective ; C3-pyrrole ; organocatalysis ; tetrasubstituted stereogenic center ; chiral phosphoric acid

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