Application of rapidly generated bidentate ligand libraries to zinc catalyzed reductions

A methodology for the combinatorial synthesis of bidentate ligands – allowing direct screening of reaction products without the need for isolation or purification – has been employed in a zinc catalyzed hydrosilylation. This reaction allowed the robustness of the methodology to be examined, by employing it in a challenging case where the metal complex is not pre-formed prior to catalysis. Four different ligand families have been examined: imines, aminals, bis-imines and oxazolines and related compounds, with a small library of each type produced and directly screened in the reaction. Three ligands providing enantioselectivities of 50% or more in this very challenging reaction were identified, and ees and conversions were equivalent whether the ligand was obtained as a crude mixture from a library synthesis or as an isolated, purified compound.

Graphical abstractParallel synthesis of bidentate chiral ligands was carried out, and employed to zinc-catalyzed hydrosilylations without any purification and with minimal manipulation. Results were consistent with traditionally formed ligands.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Rapid ligand library synthesis. ► Direct addition of crude library members to reaction medium. ► Comparable results between in-situ ligand generation/screening and traditional catalysts preparation.