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

Abstract

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,Rboxman. In contrast, the introduction of two additional methyl groups provides stereochemical control during backbone construction and thereby access to the methylated derivative Me,Rboxman, 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,Rboxmene. Subsequent complexation experiments with iron and cobalt chloride precursors afforded the four-coordinated chlorido complexes Me,RboxmanMCl2 (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 α-fluorination of β-ketoesters and oxindoles (up to 98% yield and 94% ee) demonstrated their suitability for enantioselective catalysis.

High-Yielding Flow Synthesis of a Macrocyclic Molecular Hinge

“…In the final stage of the reaction, macrocyclization is favored over oligomerization due to preorganization of the reaction intermediates. It is likely that 6 adopts a C-shaped conformation similar to the rigid geometries of the bis-oxazoline (BOX) and related “boxman” compounds, which are used as chelating ligands for asymmetric catalysis. , The methyl groups of the xylylene spacer are highly important, as reactions using the non-methylated isocyanate as a starting material produce insoluble ureas with no significant macrocycle formation (Figure S34). To rationalize this observation, DFT energies were calculated for varying conformations of 6 and its non-methylated analogue 7 , spanning all possible xylylene–oxazolidine torsion angles φ 1 and φ 2 (Figure ).…”

Asymmetric Preparation of α-Quaternary Fluorinated β-keto Esters. Review

“…Electron-rich substituents, such as the methoxy group in the aromatic ring of 1-indanone-2-carboxylate, caused slight increased the ee (Figure 3). Three new examples with other substituents in the aromatic ring were tested with Zn(II)/Boxmi and t-butyl ester giving also high levels of induction (84-92%) [54].…”

High Yielding Flow Synthesis of a Macrocyclic Molecular Hinge

“…It is likely that 6 adopts a C-shaped conformation similar to the rigid geometries of the bis-oxazoline (BOX) and related "boxman" compounds, which are used as chelating ligands for asymmetric catalysis. 71,72 The methyl groups of the xylylene spacer are highly important, as reactions using the non-methylated isocyanate as a starting material produce insoluble ureas with no significant macrocycle formation (SI, Figure 34). To rationalize this observation, DFT energies were calculated for varying conformations of 6 and its non-methylated analogue 7, spanning all possible xylylene-oxazolidine torsion angles φ1 and φ2 (Figure 10).…”