Applications of Chiral Anions in Asymmetric Catalysis

Book excerpt: The synthesis of molecules with control over their three-dimensional configuration, known as absolute stereochemistry, is one of the highest goals of synthetic organic chemists. As is so often the case, we strive to reach the facility and efficiency with which Nature achieves this goal. Fortunately, the chemist's imagination allows us to envision nearly unlimited possibilities for new modes of catalysis. In this dissertation, I discuss one branch of asymmetric catalysis that has in a short time progressed from relative obscurity to the forefront of the ever-expanding set of reactions that can be achieved stereoselectively. The basis of this strategy is ion pairing between chiral anionic species and cationic catalysts or intermediates. Chapter 1 discusses the background of the field. In particular, I examine what factors and precedent led the chemical community to recognize the potential of chiral anions to influence reaction stereoselectivity. Many different contributions skirted around the issue before people began to realize that this type of catalysis represents a distinct area that can be uniquely applicable to certain classes of transformations. The suddenness of this recognition is all the more fascinating because chiral cationic species have used in catalysis for some time. Our laboratory's first endeavor in the arena of chiral anions in documented in Chapter 2. This study dovetailed from the group's work in the area of homogeneous gold catalysis. Because many gold catalysts bear a positive charge, we questioned whether a chiral counteranion could be used to induce asymmetry. We were interested in pursuing this strategy because the traditional approach of using chiral ligands bound to the metal was not always sufficient to obtain high enantioselectivity in gold catalyzed reactions. In fact, a chiral phosphate counteranion was found to mediate certain gold-catalyzed reactions with vastly superior degrees of stereoselectivity. Additionally, chiral ligands could work cooperatively with the chiral counteranion to enable particularly challenging asymmetric reactions. After this, we moved from metal-catalyzed reactions to transformations where the chiral anion could form an ion pair with a cationic reaction intermediate. Based on some precedent, we investigated an asymmetric ring opening of meso-aziridinium ions. This transformation is ideal for testing out the ability of chiral anions because the mechanism essentially dictates that any observed asymmetric induction is a result of an ion pair interaction. Furthermore, it is a type of reaction that is not readily amenable to other forms of asymmetric catalysis because the prochiral intermediate does not possess any basic sites. Here again, a chiral phosphate performed well as a chiral counteranion, promoting the ring opening with alcohol nucleophiles in very high enantioselectivity. The method was also modified to enable an asymmetric opening of episulfonium ions. The final chapter documents a number of different efforts aimed at achieving asymmetric substitutions and additions at all-carbon electrophiles. By this time chiral anions were well established as catalysts for additions to several classes of heteroatom-stablized cationic electrophiles. However, additions to carbocations or their functional equivalents were largely out of reach. Our hypothesis was that catalysts capable of interacting covalently with carbon electrophiles could facilitate the asymmetric substitution process. Thus we examined a variety of polarizable anionic and neutral catalyst structures. While our ideas for substitutions of carbon-centered leaving groups were generally unsuccessful in producing a highly enantioselective reaction, the same concepts did lead to an asymmetric addition of amine nucleophiles to dienes. Studies of the mechanism suggested that the catalyst did in fact add covalently to the electrophile before being displaced, thereby validating our original thinking on the subject.