ANTI-INFLAMMATORY AGENTS, ANTIBIOTICS AND PHEROMONES VIA VINYL METALLOIDS

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The research proposed herein focuses upon the development of new synthetic methodology which utilizes the special directive properties of metalloidal groups to orchestrate a high degree of control on the stereochemical course which is followed in a given chemical reaction. These principles are examined with respect to classic reactions such as the Wittig olefination, asymmetric hydroboration and the directed aldol condensation. The synthesis of Z-vinylsilanes in high isomeric purity from acylsilane/ylide combinations provides the basis for new routes to trans-alkenol pheromones, and thus, illustrates the novel, complementary role played by acylsilanes compared to aldehydes in the Wittig olefination which give predominately cis products. Extension of this approach to acyltin derivatives should provide access to stereodefined vinyltin compounds which can be converted to one of the chiral aggregation pheromone components of the European elm bark beetle through an asymmetric hydroboration. Moreover, through the asymmetric hydroboration of stereo-defined beta, beta- disubstituted vinylsilanes, a new, general route to optically- active anti-inflammatory agents such as Naproxen, Ibuprofen and six related commercial products is proposed. The approach utilizes the dissymmetry of silyl vs hydrogen substituents at the reaction site to impart diastereofacial selectivity in the process which gives asymmetric induction at the more remote beta carbon. Another aspect of the research takes advantage of several new aspects of stereo-defined silylated vinylboranes which either can be converted to enolboranes which are expected to give threo-selective crossed aldol products with aldehydes, reactions which lead to polyoxygenated antibiotics. On the other hand, new concepts in sterically-directed crossed aldol reactions of acylsilanes either from the standpoint of E-enolates of acylsilanes or from enolate- acylsilane combinations are expected to enhance the scope of the now-general aldol route to these antibiotics. Thus, the thrust of this study is to decisively demonstrate by example the important role that can be played by a metalloidal group in directing the precise course followed in important chemical reactions. Moreover, in the reactions selected for study herein, the basis for further developments will be laid so that the chemical principles learned can be applied to new synthetic targets in the future.