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One‐Pot Cascade Transformation of Glucal into Structurally Diverse Drug‐Like Scaffolds
Author(s) -
Yao Hui,
Willam Ronny,
Wang Siming,
He Jingxi,
Guo Tai,
Liu XueWei
Publication year - 2019
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201900844
Subject(s) - glucal , aniline , indoline , chemistry , combinatorial chemistry , cascade , catalysis , lewis acids and bases , stereoselectivity , transformation (genetics) , phenacetin , cascade reaction , organic chemistry , biochemistry , chromatography , gene
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 3 acted as the Lewis acid catalyst. By altering InBr 3 to Ln(OTf) 3 , the indoline‐fused products could be further converted into tetrahydroquinoline‐fused cyclopentenones via ensuing retro‐ene rearrangement.