Expanding the Boxmi Ligand Family: Synthesis and Application of NON and NSN Ligands

Two synthetic strategies for a new family of neutral NON ligands featuring a bis(oxazolinylmethylidene)-isobenzofuran framework (boxman) are reported. A Pd-mediated cyclization reaction forming the isobenzofuran core constitutes the key reaction in the eight-step synthetic route to the nonbackbone-methylated target compound (H,R)boxman. In contrast, the introduction of two additional methyl groups provides stereochemical control during backbone construction and thereby access to the methylated derivative (Me,R)boxman, which was synthesized in five steps and improved yields. In addition, the synthetic sequence was transferred to the thio analogue, providing access to the NSN ligand (H,R)boxmene. Subsequent complexation experiments with iron and cobalt chloride precursors afforded the four-coordinated chlorido complexes (Me,R)boxmanMCl(2) (R = Ph, iPr; M = Fe, Co) and established the boxman family as trans-chelating, bidentate bis(oxazoline) ligands. Application of the latter in the nickel(II)- and zinc(II)-catalyzed alpha-fluorination of beta-ketoesters and oxindoles (up to 98% yield and 94% ee) demonstrated their suitability for enantioselective catalysis.