Cinchona‐Based Organocatalysts for Desymmetrization of meso ‐Compounds and (Dynamic) Kinetic Resolution of Racemic Compounds

Abstract

The desymmetrization of meso-compounds is a very useful method of preparing enantioenriched molecules from achiral compounds in a single step. In dynamic kinetic resolution (DKR), it is also possible to convert the racemic reactant with 100% completion because both (reactant) enantiomers engage in chemical equilibrium and exchange. In this way, the faster reacting enantiomer is replenished in the course of the reaction at the expense of the slower reacting one. Over the last few decades, remarkable scientific achievements have been made in these research areas by using a variety of enzymatic and nonenzymatic approaches. Among them, in many cases, the naturally occurring cinchona alkaloids and their derivatives have been shown to be superior in terms of both their catalytic activity and their selectivity. Some reactions (e.g., the alcoholytic desymmetrization of cyclic anhydrides) have already reached the level of large-scale synthetic practicability as regards the catalyst activity and enantioselectivity. The key structural feature responsible for their successful utility is the presence of the Lewis basic quinuclidine nitrogen and Lewis acidic substituents at the C9-position, such as hydroxyl, thiourea, and sulfonamide groups.In this chapter, we attempt to review the current state of the art in the applications of cinchona alkaloids and their derivatives as chiral organocatalysts in these research fields. In the first section, the results obtained using the cinchona-catalyzed desymmetrization of different types of meso-compounds, such as meso-cyclic anhydrides, meso-diols, meso-endoperoxides, meso-phospholene derivatives, and prochiral ketones, as depicted in Scheme 11.1, are reviewed. Then, the cinchona-catalyzed (dynamic) kinetic resolution of racemic anhydrides, azlactones and sulfinyl chlorides affording enantioenriched a-hydroxy esters, and N-protected a-amino esters and sulfinates, respectively, is discussed (Schemes 11.2 and 11.3).