The intramolecular anionic migration of a silyl group from a carbon atom to an oxygen atom, commonly known as the Brook rearrangement, has recently emerged as a useful synthetic tool. The proposed research involves the development of novel Brook rearrangement-mediated tandem reactions, or those combining the rearrangement with bond-forming steps that precede and/or follow the silyl migration event. A particular objective of the proposed research is to develop applications in which the silyl group not only facilitates multiple bond-forming steps, but also provides opportunities for overall stereocontrol. Applications that meet this goal will further the mechanistic understanding of the Brook rearrangement and cultivate practical syntheses of medicinally important compounds. The specific goals of the research program are the development of silyl migration-mediated bis-functionalizations of arene chromium tricarbonyl complexes and silyl migration-mediated Baylis-Hillman reactions. The silyl migration-mediated bis-functionalization of arene complexes entails initial nucleophilic addition to ortho-silyl substituted benzaldehyde complexes, followed by silyl migration and inter- or intramolecular electrophilic trapping of the resultant aryl anion. It is proposed that the use of sllacyclobutanes will improve the stereoselectivity by coordinating the neighboring aldehyde carbonyl and enforcing approach of the nucleophile from a single rotamer. This strategy, in combination with an asymmetric Dotz benzannulation for the preparation of the arene complex precursors, will provide key steps for an asymmetric total synthesis of the antitumor antibiotic compound fredericamycin A. The tertiary amine-catalyzed condensation of aldehydes with activated olefins, known as the Baylis-Hillman reaction, provides an elegant and efficient method to construct densely functionalized compounds. Preliminary results demonstrate that alpha-substituted activated olefins participate in this transformation and alleviate polymerization and reversibility problems that otherwise plague the method. On the basis of these results, a study of stereoselective silyl migration-mediated Baylis-Hillman reactions is proposed, along with the application of the method towards solid-phase synthesis.
