New Preparation of Tridentate Bis-oxazoline Carbazole Ligand Effective for Enantioselective Nozaki-Hiyama Reaction

A new preparation of the tridentate bis-oxazoline carbazole ligand 1 is described.This method features direct formation of the amide, which is a precursor of the ligand 1, via the Pd-catalyzed amidation and following BF 3 •OEt 2 mediated oxazoline formation.This method required only 2 steps from the aryl iodide to form the bis-oxazoline ligand; hence, it would be generally used for preparing other bis-oxazoline ligands.Nozaki-Hiyama reactions, Cr(II)-mediated C-C bond-forming reactions developed by Nozaki et al., have been well studied and developed by many research groups because of their potential utility. 1 Indeed, numerous total syntheses of complex natural products employed these reactions, proving their high chemoselectivity and excellent compatibility with various functional groups. 2However, because a large amount of chromium (II) salts must be used to complete these reactions, 2 a method for reducing this amount has been explored.In 1996, Fürstner et al. reported the catalytic redox system which successfully reduced the quantity of chromium salts, and since then, the Cr(II)-mediated C-C bond-forming reactions have been more valuable 3 and their asymmetric catalysis has drawn much attention.Cozzi and Umani-Ronchi reported the first catalytic asymmetric Nozaki-Hiyama allylation using a commercially available salen ligand, 4 but the enantioselectivities and yields were not satisfactory.In addition, the formation of a considerable amount of the side-product derived from a pinacol coupling was also a problem.To overcome these difficulties new chiral ligands for Nozaki-Hiyama reaction have been developed by several research groups, 5 and we have independently reported a newly developed tridentate bis-oxazoline