Abstract

The Development of Synthetic Supramolecular Hosts as Mechanistic Probes and Selective Catalysts

ByMariko Morimoto Doctor of Philosophy in Chemistry University of California, Berkeley Professor F. Dean Toste, Co-Chair Professor Kenneth N. Raymond, Co-Chair

Chapter 1. An overview of various supramolecular hosts and their application as synthetic catalysts is presented. Particular emphasis is placed on more recent advances in the field, ranging from organic and organometallic reactivity, through site-selective modifications, to challenging photochemical reactivity enabled by these hosts. By introduction of the various modes of catalytic reactivity, the unique advantages of non-covalent, macromolecular catalysis as a synthetic tool and its powerful potential for practical applications are discussed. Chapter 2. The effects of host structural features on supramolecular catalysis are experimentally determined by employing a series of [M4L6]n- hosts as mechanistic probes. The synthesis of a novel supramolecular [Si4L6]8- host is first described, which serves as an isostructural analogue to [Ga4L6]12- Raymond tetrahedron differing only in overall charge. Through a number of parallel kinetic experiments, the specific role of host charge on the efficacy of microenvironment catalysis is quantitatively determined. Next, the syntheses of catalytically active [In4L6]12- and [Ge4L6]8- hosts are presented, and the effect of altering the metal vertices on host reactivity is elucidated. This work represents the first example of a thorough investigation that connects discrete structural components of a synthetic supramolecular catalyst to specific mechanisms of reactivity. Chapter 3. Challenging oxidative addition reactions of iodoarenes across CuI and PdII organometallics facilitated by the [Ga4L6]12- Raymond tetrahedron under unusually mild, room temperature conditions are described. Atypical reactivity and selectivity are observed among regio-isomeric iodotoluene substrates, which demonstrate that the transformation is specific to strongly bound guests. Background reactivity in the absence of host is assessed by a series of control experiments with various solvents and additives, which result either in no observable reactivity or degradation of the starting material. This lack of observable background reactivity is indicative of a rare circumstance in which the host not only accelerates but alters the lowest energy reaction pathway of an organometallic reaction from that in bulk solution. Chapter 4. A series of chemo- and site-selective reduction reactions mediated by the Raymond tetrahedron using a pyridine borane reductant are described. The host-catalyzed reaction demonstrates an unusually broad substrate scope for small molecule reduction, including ketones, enones, oximes, hydrazones, and imines. Furthermore, reactivity is maintained for partially encapsulated pendant carboxylate substrates, which enables high ε-selective reductive amination of lysine with a variety of halogenated benzaldehyde electrophiles. Inspired by the post-translational modification of complex biomolecules by enzymatic systems, this supramolecular reaction is then applied to the lysine-selective labeling of peptides and proteins.