Diverse Mechanistic Approaches to [4 + 2] and [2 + 2] Cycloadditions by Transition Metal Photosensitization

Organic photochemistry enables the rapid synthesis of complex structures that are often difficult to access by other reaction types. The work described herein has capitalized on three mechanistically distinct modes of photoactivation for the synthesis of a variety of heterocyclic and carbocyclic scaffolds. Chapter 2 describes the development of a hetero-Diels--Alder cycloaddition of bis(enone) substrates that operates under visible light photoredox catalysis. Single-electron reduction inverts the polarity of one of the enone coupling partners to facilitate the electronically mismatched cycloaddition. In all cases, the reaction generates a single constitutional isomer with high diastereoselectivity. Chapter 3 describes the development of a visible light promoted [2+2] cycloaddition of conjugated 1,3-dienes that operates by energy transfer sensitization. The scope of the reaction is broad and complementary to the radical ion cycloadditions previously developed in our group. The synthetic utility of this method was illustrated in a concise synthesis of the cyclobutane-containing natural product epiraikovenal. Chapter 4 describes preliminary efforts towards the development of an enantioselective copper-catalyzed [2+2] cycloaddition. Our strategy involves the use of chiral, non-coordinating counterions to mimic the electronic and photophysical properties of the highly cationic copper catalysts typically employed in the racemic reaction. Although the levels of enantioselectivity achieved to date are modest, these proof-of-concept results represent the first catalytic, asymmetric approach to this class of reactions.