ASYMMETRIC BIOCATALYTIC METHODS ENABLED BY VISIBLE LIGHT-PROMOTED RADICAL PROCESSES OUTSIDE AND INSIDE ENZYME ACTIVE SITES

Abstract

The use of enzymes as catalysts in organic synthesis has long been sought due totheir abilities to catalyze reactions with unparalleled levels of selectivity and efficiency. In the past three decades, biocatalysis has witnessed significant growth due to several key advances in molecular biology that have made biocatalysts more accessible and modular. Now, biocatalysis has established itself at the forefront of catalysis as a disruptive, forward thinking platform for the construction of societally important compounds. Concomitantly, there has been an exponential growth in the use of visible light to promote chemical reactions. Visible light can be utilized to invoke unique and complementary reactivities often through the generation of free radical intermediates. Prominent among the various methods for photoinduced reactivity are photoredox catalysis and reactions involving the direct photoexcitation of charge transfer complexes. Recently, there have been a number of successful synthetic strategies combining photoinduced reactivity with enzyme catalysis. Efforts exploring this synergistic merger have unlocked powerful organic transformations that would not be possible with either activation platform alone. This dissertation describes the development of two distinct strategies that combine photochemistry and biocatalysis for novel asymmetric reactions. The first strategy, discussed in Chapter 2, describes how photoredox catalysis can enable the racemization of traditionally inert stereocenters. These racemizations can then be conducted in the presence of enzymes to afford novel dynamic kinetic resolutions. Chapter 3 discusses the second strategy involving the photoexcitation of charge transfer complexes formed in the active sites of ‘ene’-reductases to induce non-natural intermolecular asymmetric C–C bond-forming reactions between α-chloroamides and alkenes.