Solid-phase synthesis of supported multidentate phosphorus ligands

: a modular and versatile approach

Abstract

Homogeneous asymmetric catalysis offers a powerful tool which provides access to enantiomerically pure compounds. Still, in spite of decades of research, only a handful of so- called privileged ligands are known which exhibit high selectivity and activity in a wide range of reactions. The discovery of new high performance catalysts relies heavily on trial-and-error. Yet, there still is a lack of efficient combinatorial methods which enable the synthesis and screening of vast and diverse ligand libraries.

Solid-phase synthesis (SPS) represents an effective methodology towards ligand libraries. Using this approach, ligands can be synthesized step-by-step while being supported on a resin bead. This has as a main advantage that it can greatly simplify ligand purification and often only a filtration step is required. By employing SPS in a combinatorial manner, facile access towards large supported ligand libraries can be obtained. An additional advantage when using a solid support is the potential ease of catalyst recovery and recycling in subsequent catalytic reactions. In contrast, catalyst recovery often represents a large problem in homogeneous catalysis. While quite a number of monodentate phosphorus ligand libraries are known, multidentate libraries still remain scarcer. This can mainly be attributed to their inherently more difficult synthesis and work-up.

An efficient solid-phase synthetic approach for the synthesis of supported multidentate phosphorus ligands is reported in this thesis. This highly modular methodology offers facile access to structurally diverse ligand libraries in high yields requiring only minimal work-up procedures. The presented approach is highly versatile and a whole host of different types of multidentate phosphorus ligands are accessible from one immobilized starting synthon.

Solid-phase synthetic strategies towards four main classes of supported phosphorus ligands are reported: diphosphines (chapter 2), phosphine-phosphites (chapter 3), PN and PNN-ligands (chapter 4) and tripodal phosphine ligands (chapter 5). These supported ligand libraries have been successfully applied in various catalytic reactions ranging from asymmetric hydrogenation and ester hydrogenation to the cleavage of lignin model compounds. Finally the recoverability and recyclability of these immobilized ligands has been investigated under both batch and flow conditions.

Date of Award	30 Nov 2016
Original language	English
Awarding Institution	University of St Andrews
Supervisor	Paul C J Kamer (Supervisor)