| Description |
Palladium-catalyzed alkene difunctionalization reactions represent a powerful methodology for the construction of diverse carbon-carbon and carbon-heteroatom bonds. The success of these transformations requires the effective stabilization of alkyl- Pd intermediates generated following migratory insertion of an alkene. Stabilization of Pd-intermediates helps to prevent side reactions, thus enabling the formation of desired difunctionalization products in high selectivity. Chapter 1 examines distinctive methods used for the interception of alkyl-Pd intermediates and the strategies associated with minimizing byproduct formation. The Sigman laboratory has been interested in alkene difunctionalization reactions that take advantage of the unique reactivity of n-allyl/benzyl stabilized intermediates in order to generate significant molecular complexity from simple starting materials. Chapter 2 details the development of the Pd-catalyzed 1,4-difunctionalization of the commodity chemical 1,3-butadiene, which affords difficult to access skipped polyene products. This transformation regioselectively functionalizes the two terminal alkenes of 1,3-butadiene by means of a a ^ n ^ a isomerization of cationic Pd-intermediates. The utility of the 1,4-difunctionalization of 1,3-butadiene is highlighted by the synthesis of a highly functionalized skipped triene-containing fragment of ripostatin A. Chapter 3 describes an advancement of the 1,4-difunctionalization reaction, namely using isoprene as the 1,3-diene substrate to generate skipped diene-containing terpenoid products. This method presents an added challenge resulting from the use of a 1,3-diene with two inequivalent alkenes that can contribute to complex isomeric product mixtures as the result of unselective alkene insertion. Through the use of pyridineoxazoline- type ligands, good site selectivity of alkene insertion has been achieved. Mechanistic studies that combine design of experiments with systematic multiparameter ligand modulation ultimately suggest that the electronic asymmetry and steric properties of the ligand are critical to the observed enhancement in site selectivity of alkene insertion. The development of a 1,3-difunctionalization of terminal alkenes using 1,1- disubstituted vinyl triflates and boronic acids is discussed in Chapter 4. This transformation is realized using a novel difunctionalization strategy, and generates a new C(sp2)-C(sp2) double bond as well as a C(sp3)-C(sp2) bond. Dependent on the boronic acid coupling partner, the reaction affords skipped diene or allylic arene products stereoand regioselectively. |
