Nickel-catalyzed efficient asymmetric synthesis of chiral chromans with quaternary allylic siloxanes and their antitumor activity is reported for the first time. A P-chiral monophosphine ligand (R)-AntPhos was found to be the ideal ligand to form a series of tertiary allylic siloxanes bearing chroman structures with excellent yields, enantioselectivities and E/Z selectivity using triethylsilane as the reductant. This reaction has a broad substrate scope and provides a practical way to synthesize useful chroman derivatives with chiral tertiary allylic alcohols. Up to 69 examples were successfully established with this method. A series of 3-hydroxychroman derivatives were obtained and tested for anti-tumor activity. Number of compounds showed good anti-tumor activity, less toxicity to reference cell, and specificity to different cancer cells, which could be new anticancer leading compounds. The configuration and substituent of the 3-hydroxychromans has big effects for their anti-tumor activity. Further study on structure-activity relationships of these 3-hydroxychromans is under investigation to discover new anti-cancer drugs.
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Methods and procedures, HPLC, NMR