One-Pot Cascade Transformation of Glucal into Structurally Diverse Drug-Like Scaffolds.

One-Pot Cascade Transformation of Glucal into Structurally Diverse Drug-Like Scaffolds.

Yao, Hui;Willam, Ronny;Wang, Siming;He, Jingxi;Guo, Tai;Liu, Xue-Wei;
Chemistry, an Asian journal 2019
224
yao2019onepotchemistry

Abstract

A diversity-oriented synthesis strategy to produce three types of structurally drug-like N-heterocyclic-fused rings has been developed from abundant biomass-derived d-glucal, aniline and water in a stereoselective manner. The overall transformation which entails a cascade of Ferrier reaction and 4π conrotatory imino-Nazarov cyclization was performed in one-pot allowing convenient preparation of scaffolds of high molecular complexity from relatively simple starting materials. While indoline-fused products were readily accessible using ortho-unsubstituted secondary anilines as substrates, reactions with ortho-hydroxyl-anilines furnished fused 1,4-benzoxazines instead. In both cases, InBr acted as the Lewis acid catalyst. By altering InBr to Ln(OTf) , the indoline-fused products could be further converted into tetrahydroquinoline-fused cyclopentenones via ensuing retro-ene rearrangement.

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