一种具有手性联二萘骨架新型TADDOL配体的合成

Synthesis of a Novel TADDOL Type Chiral Ligand with a Binaphthyl Backbone

以3 羟基萘 2 甲酸甲酯4为原料,通过Cu(II)催化的酚氧化偶联、外消旋化合物的拆分和格氏反应等关键步骤,经7步反应以25%的总收率合成了一种具有手性联二萘骨架的新型TADDOL配体12,其光学纯度达到98%.

The TADDOLs are a class of chiral ligands which have attracted considerable attention in recent years.They have been widely used in asymmetric synthesis as chiral ligands for a number of asymmetric reactions.The preparation of a novel TADDOL type chiral ligand 3 (Ar=Ph) with a binaphthyl backbone is reported in this paper.The synthesis of this novel ligand started from methyl 3-hydroxy-naphthyl-2-carboxylate 4 by Cu(II) catalyzed oxidative coupling under an oxygen atmosphere.Resolution of the coupled racemic binaphthyl 5 by diastereo-derivatization salt formation followed by basification and acidification afforded the binaphthyl diacid (R)-9 with over 98% ee as determined by optical rotation and compared with the reported data.(R)-9 was converted to its bis-methyl ester (R)-5 by treatment with diazomethane in quantitative yield.The bis-methyl ester was further protected on the phenol hydroxy group by treatment with (chloromethyl)methyl ether (MOM-Cl).Further reaction of (R)-10 with excess phenyl magnesium bromide afforded the tetraphenyl diol (R)-11 in 84% yield.Final removal of the MOM protection by treatment with p-toluenesulfonic acid gave the required ligand (R)-12 in 65% yield.This synthesis was achieved in seven major reaction steps with an overall yield of 25% and the optical purity of ≥98%ee.The application of this ligand for asymmetric reactions will be reported in due course.