C2-Symmetric chiral bis(oxazoline)–metal complexes in catalytic asymmetric synthesis

Abstract

The development of methodologies for efficient asymmetric synthesis is one of the most important areas of synthetic organic chemistry.1 The syntheses of biologically relevant natural and unnatural organic molecules in optically pure form are of central interest in medicinal chemistry and related disciplines. Variations in the stereochemistry of molecular probes for a target enzyme or receptor sites very often display dramatic differences in their binding properties and biological activities. For meaningful biological studies it is important, if not mandatory, to synthesize such agents in enantiomerically pure form. Recent advances in molecular biology and modern instrumentation techniques have led to a better understanding of many complex human diseases at the molecular level. Concurrent with these remarkable achievements have come new challenges and opportunities for asymmetric synthesis. Thus, from the design of enzyme inhibitors to the synthesis of receptor agonists or antagonists and bioactive natural products, asymmetric synthesis is of fundamental significance in biology and medicine. The advances in asymmetric synthesis have now reached the point that many organic molecules can be prepared with near complete enantioselectivity. This technology is particularly sophisticated in the generation of new stereogenic centers in the presence of existing chiral centers. A number of asymmetric catalysts or so called ‘abiological catalysts’ are approaching an efficiency and selectivity comparable to enzymes such as in the asymmetric hydrogenation of dehydroamino acids utilizing chiral bisphosphine–rhodium complexes,2 asymmetric isomerization of allylic amines with rhodium(I)–BINAP complexes,3 asymmetric epoxidation of allylic alcohols,4 asymmetric epoxidation of unfunctionalized olefins,5 asymmetric reductions with chiral oxazaborolidenes6 and asymmetric dihydroxylation reactions.7 The advantage of abiological catalysts, however, is the availability of either enantiomer of the catalyst which enables one to synthesize either enantiomer of the target molecule. Today there is enormous emphasis on the design and development of efficient chiral catalysts for enantioselective synthesis and this field has become one of the most intense areas of organic chemical research. In recent years, C2-symmetric chiral bis(oxazoline) ligand–metal complexes have received a great deal of attention through their use in various catalytic process.1c The bis(oxazoline) ligands are structurally related to C2-symmetric semicorrins pioneered by Pfaltz and co-workers.8a–c The inception of bis(oxazoline) ligands, however, added a new dimension in terms of flexibility in ligand design, convenient synthesis and availability of ligands in both enantiomeric forms. Since the early 1990s, many impressive enantioselective carbon–carbon bond forming reactions, aziridination reactions, hydrosilylations, oxidations and reductions have been recorded using bis(oxazoline)–metal complexes. The present review is intended to focus on the recent developments of bis(oxazoline) ligand–metal catalyzed asymmetric reactions and their applications in organic synthesis. The authors do not intend to provide an exhaustive review of this area since earlier developments have been reviewed by Pfaltz8a–c and Bolm.9 Applications of mono- and tris(oxazoline) ligand–metal complex catalyzed reactions are not included in this review.