The biomimetic total synthesis of (+/-)11-O-debenzoyltashironin

This thesis describes the total synthesis of 11-O-debenzoyltashironin and analogs thereof.; Chapter 1 provides an overview of neurodegenerative disease and neurotrophic factors. This chapter offers background and contextualizes the research described herein.; Chapter 2 describes the regioselectivity of subset of Diels-Alder reactions conducted during an oxidative dearomatization/intramolecular Diels-Alder sequence. These reactions involve the use of ortho-alkoxy phenols under the influence of hypervalent iodine in the presence of either allenyl or allyl alcohols. In the sequence, the hypervalent iodine serves to oxidatively dearomatize the phenol with concomitant trapping of the alcohol. These ortho-quinone monoketals contain a 1,3-diene system that is optimally aligned with the pendant olefin to undergo an intramolecular Diels-Alder reaction. This chapter delineates an interesting internal electronic bias of the investigated systems that allows the practitioner to choose the regioselective outcome of the Diels-Alder through the judicious choice of dienophile (i.e. allenyl vs. allyl alcohol).; In chapter 3, a series of oxidative dearomatization/Diels-Alder reactions are described whereby a single methyl group determines the stereochemical outcome of the cyclization reactions. The synthesis of numerous cycloaddition precursors is performed using a common aromatic progenitor. The commonality of these compounds lies in the tethering of the dienophile to the phenol undergoing oxidation. This all-carbon tether possesses a single methyl stereocenter alpha to the aromatic ring system. When the phenol is oxidized with hypervalent iodine, the methyl group dictates the course of the cyclization event to consistently provide cycloadducts with the methyl on the concave face of the molecule. This event is examined in a number of cases, and the stereochemical course of the reaction is confirmed through X-ray crystal analysis.; Chapter 4 outlines the total synthesis of the putative neurotrophic factor 11-O-debenzoyltashironin. The synthesis employs the oxidative dearomatization/Diels-Alder cascade examined in the previous two chapters to produce all four rings of the natural product in a single transformation. In the event, four quaternary carbons (three of them being all-carbon quaternary carbons) are formed from a relatively simple phenol precursor. After the oxidative dearomatization/Diels-Alder step, a series of substrate-controlled reactions install the remaining stereocenters with impressive diastereoselectivity.