Applications of palladium catalyzed asymmetric allylic alkylation: The synthesis of quaternary amino acids and efforts toward the total synthesis of terpestacin

This work describes the application of palladium-catalyzed asymmetric allylic alkylation for the preparation of quaternary amino acids and as part of an approach to the total synthesis of the sesterterpene terpestacin (2-1).; Chapter 1 gives an overview of strategies that have been used to prepare macrocyclic natural products through the formation of a carbon-carbon single bond. These strategies are organized according to the type of carbon-carbon single bond being formed in the macrocyclization.; In chapter 2, a synthetic approach to the complex natural product terpestacin (2-1) is discussed which begins with the O-allylation of 3-methylcyclopentane-1,2-dione (2-51) with isoprene monoepoxide (2-52). This reaction proceeded in high yield and enantioselectivity to provide the expected alcohol which was subsequently protected and subjected to Claisen rearrangement conditions to transfer the allyl chain to the adjacent carbon, thereby providing the C1 quaternary carbon of terpestacin ( 2-81). An investigation of the optimal approach for introduction of [3-(5-benzenesulfonyl-3-methylpent-3-enyl)-2-methyloxiranyl]methanol ( 2-46) is detailed and culminates in the preparation of the acyclic macrocyclization precursor (2-94). Strategies employing an allyl enol ether as a latent C23--C25 side chain were abandoned due to chemoselectivity concerns and investigations to find a suitable protecting group for the cyclic enol are detailed. An investigation of the proposed macrocyclization is presented. The suitably protected macrocyclization precursor (2-157) for the total synthesis of terpestacin has been obtained in 10 longest linear steps. Completion of this synthesis requires macrocyclization and introduction of the C23--C25 alcohol side-chain.; Chapter 3 provides a comprehensive review of the heterocyclic scaffolds that have been used to prepare quaternary amino acids. These examples are organized according to the scaffold ring size.; Chapter 4 details the use of oxazinones lacking a chiral control element as heterocyclic scaffolds to prepare quaternary amino acids by means of palladium-catalyzed asymmetric allylic alkylation. The synthesis and use of a variety of 5-alkyl- or 5-aryl-3,6-dihydro-[1,4]-oxazin-2-ones are described. The reaction scope was examined for cyclic and non-cyclic electrophiles. Additionally, the acceptable range of substituents at the reacting carbon center was investigated. Yields were generally high with enantioselectivities around 70% for simple acyclic allylation and as high as 99% for cyclic electrophiles.