Organosilicon-Based Cross-Coupling Reactions

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DESCRIPTION: (provided by applicant) The basic objectives of this application are the development and application of a newly invented silicon-based carbon-carbon bond forming reaction. This program is divided into three sections: the first and major effort will be methodological exploration of the new process, the second will be the investigation of the mechanism and origin of activation, and the third will be the application of the reaction to the synthesis of selected targets that illustrate the power of the technology. The methodological program is the most extensive and is subdivided into many projects. The first involves the exploration of the general features of the reaction such as the nature of the silicon substituents, the spectator groups, the catalyst, and additives. An important subgoal is the development of procedures that do not require the addition of fluoride activators. Next, the ability to install silicon into various organic skeletons will be developed with new reaction chemistry. The second and most ambitious part of the methodological study is the exploration and development of the various structural scenarios in which the silicon cross coupling process can function, for example: cyclopropyl-, oxiranyl-, alkynyl-, aryl-, heteroaryl-, and most importantly alkenylsilanols. Many of these ventures will require the development of new methods for introducing the silicon functionality. Included in this section will be the examination of the scope of organic electrophilic components that will serve as partners in the cross-coupling reaction such as chlorides, triflates and phosphates. The section on mechanistic studies will focus on establishing the rate equation, the role of ligands on the palladium catalyst and particularly on the origin of activation of the silicon unit by the external activators. Our focus will be to identify the molecular detail at the critical transmetalation step. The synthesis targets to be tackled belong to a wide range of natural product families. Since the carbon-carbon forming reaction under development herein is widely general for many structural types, the selection of synthetic challenges is mostly driven by the successes achieved in the methodological section. Synthetic approaches to leukotriene A4 the calyculin A tetraene sidechain, indole alkaloids and the C-arylglycoside papalucandin D are detailed.