engleski

Stereoselective Organocatalytic Synthesis of α-Triarylmethanamines via Formal Betti Reaction

A stereoselective synthesis of α- triarylmethanamine structural motifs via formal Betti reaction is described. Chiral α- triarylmethanamines are represented as ubiquitous building blocks found in a variety of natural products and biologically active molecules. Preparation of such compounds has been challenging due to the steric hindrance positioned at the newly formed center of chirality. The catalyst has inherent difficulty in controlling the enantioselectivity of the arylation of ketimines derived from diaryl ketones due to the lack of sufficient steric difference between the two aryl rings. Synthesis of such optically active compounds relies on the usage chiral organometallic complexes of transition metals, such as Rh(I), Pd(II), Ni(II), Zn(II) and Co (II). On the other hand, to the best of our knowledge, there are no reports on the organocatalytic approach to the synthesis of these valuable motifs. Herein, we report a chiral Brønsted acid- catalyzed formal Betti reaction between diaryl ketimines and phenols for the asymmetric construction of α-triarylmethanamines. This type of reaction proceeds via direct 1, 2- addition of variously substituted phenols to imines resulting in enantioenriched α- triarylmethanamines. The success of this transformation may be attributed to the in situ generation of the reactive iminium species from 3-hydroxysubstituted isoindolinones which makes them susceptible to a nucleophilic attack (Scheme 1). The reaction proceeds in a highly regioselective and enantioselective fashion, showing a broad tolerance of functionalities both in the aromatic ring of the isoindolinone alcohol, as well as on phenol. The absolute configuration of the major enantiomer was unambiguously determined to be (R) by single crystal X-ray diffraction analysis. Based on this result, the stereochemical induction in the products stems from the nucleophilic attack of the phenol from si face of the electrophile.

stereoselective synthesis ; organocatalysis ; triarylmethaneamine

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