engleski

Stereoselective Synthesis of α-Quaternary Methaneamines via Formal Betti Reaction Catalyzed by Chiral Brønsted Phosphoric Acid

Chiral α-quaternary methanamines are common structural motifs found in a variety of natural products exhibiting wide spectrum of biological activities. Synthesis of such compounds has always been challenging because of the steric hindrance positioned at the newly formed center of chirality. The most common strategies for the construction of this class of optically active compounds is well described and mostly relies on usage of chiral transition-metal complexes, e.g. Rh(I), Pd(II), Ni(II), and Co(II). However, to the best of our knowledge, there is no literature precedent for the preparation of quaternary α- triarylsubstituted methanamines based on stereoselective organocatalytic reaction. In this respect, we developed a catalytic formal Betti reaction with stereoselctivity induced by chiral Brønsted phosphoric acid. This type of reaction proceeds via direct 1, 2-addition of phenols to imines resulting in enantioenriched α- triarylmethanamines. Key to success of this transformation lies in the in situ generation of the reactive iminium species from 3- hydroxysubstituted isoindolinones. Various phenols added smoothly, enabling the synthesis of a variety of α-triphenylmethylamines in up to 96% isolated yield, and up to 99% ee. Functional group tolerance with respect to isoindolinone alcohols, as well as to phenols, will be presented.

stereoselective synthesis ; quaternarny stereogenic center ; organocatalysis

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