Meerwein-Ponndorf-Verley Reductions and Oppenauer Oxidations: An Integrated Approach

The reaction mechanism of Meerwein-Ponndorf-Verley-Oppenauer (MPVO) reactions proceeds in most cases via a cyclic six-membered transition state in which both reductant and oxidant are coordinated to the metal centre of a metal alkoxide catalyst. Thermodynamics gives insight into the strength of reductants and oxidants and yields quantitative information about equilibrium conversions that may be reached in a specific MPVO reaction. In aluminium-catalysed MPVO reactions, ligand exchange dominates the rate of reaction. In lanthanide-catalysed MPVO reactions, ligand exchange is much faster and reaction rates, therefore, are determined by either ligand exchange, hydride transfer, or both. Traditional aluminium catalysts usually show too slow ligand exchange to enable the use of catalytic amounts. Alkali and alkaline-earth metals have very high ligand exchange rates, but low charge density (Na, K) or low coordination number (Li) mostly prevents catalytic use in this case, too. Promising results are reported for lanthanide catalysts and zirconium complexes and their hafnium analogues, in which good Lewis acidic character is combined with excellent ligand exchangeabilities. Metal alkoxide catalysts can be prepared by several methods. Direct synthesis proceeds via metals or anhydrous metal halides. Exchange of the alkoxide group can be achieved by alcoholysis or transesterification. Several heterogeneous systems have been developed, with advantages like easy catalyst handling, workup, and recycling. Here again, lanthanide and zirconium catalysts seem very promising. Various examples of selective reactions are given. Chemo- and regioselectivity were found almost immediately after discovery of the MPVO reactions, especially in the synthesis of steroids and other bio-related compounds. Elegant modern examples show regio- and stereoselectivity in various forms. Recently, highly enantioselective MPV reduction has been reported, in which the catalyst was a chiral lanthanide(III) alkoxide. 1. Introduction 2. Mechanism and Related Reactions 2.1. Reaction Mechanism 2.2. Side Reactions 3. Thermodynamics, Selection of Oxidants and Reductants 4. Metal Alkoxide Catalysts 4.1. Choice of the Metal Ion, the Ligands, and the Solvent 4.2. Preparation and Characterisation 5. Heterogeneous Catalysts 6. Selectivity in MPVO Reactions 6.1. Chemo- and Regioselective MPVO Reactions 6.2. Stereoselective MPVO Reactions 6.3. Enantioselective MPVO Reactions 7. Conclusions