Borane-Appended Ligand Design Strategies for Small Molecule Capture and Reactivity

Abstract

In nature, metalloenzymes act as the premier catalysts for small molecule activation and transformation. The high activity and selectivity of enzymatic processes are, in part, owed to the complex system of acidic residues that make up the secondary and tertiary structures surrounding metal active sites. Synthetic systems that mimic these interactions, by employing either Brønsted or Lewis acids, can be used to gain further insight into small molecule transformations. The results described herein build upon existing literature of intramolecular ligand systems that feature moderately acidic Lewis acids that are pre-organized to interact with target metal-substrate complexes. In this thesis, metal-ligand complexes incorporating secondary sphere borane Lewis acids are presented. Two ligands have been prepared: 1) a bidentate pyridine-pyrazole ligand framework that bears an appended trialkylborane at varied tether lengths from the metal center (explored in chapter 2 and chapter 5) and 2) a tridentate, tetrahedral enforcing 1,4,7-triazacyclononane ligand framework that bears an appended trialkylborane with a 3-carbon tether length (explored in chapter 3, chapter 4, and chapter 5). Metalation with first-row transition metals Zn(II), Fe(II), Cu(I), and Co(II) resulted in a series of intramolecular transition metal-borane platforms that were employed for the capture and transformation of biologically and industrially-relevant small molecules. The Zn(II)-N2H4 complexes investigated in chapter 2 provide important insight into the effect of Lewis acid binding to reactive substrates that contain acidic N-H peaks: additive Lewis acid effects from the metal center and appended borane lower the acidic group’s pKa, making deprotonation accessible. Reactions to transform hydrazine at Zn(II) and Fe(II) highlight the importance of flexibility in the system when a 3-carbon appended Lewis acid tether is employed. The importance of flexibility in this system is extended to the weakly basic substrate thiophenolate in chapter 5, where the 3-carbon tether is once again highlighted as the ideal length for an intramolecularly appended Lewis acid to form a cooperative interaction with the metal-bound substrate. The chemical insight gained through these substrate binding studies was extended to the Cu(I) system explored in chapter 3. Importantly, the appended borane within the secondary coordination sphere enables capture of an otherwise unstable copper hydride. Reactivity investigations with this novel complex uncovered divergent reaction pathways that can be accessed by tuning the Cu oxidation state and, ultimately, a unique mechanism for phenylacetylene reduction was discovered. Chapter 4 extends the reactivity of intramolecular borane-bound metal hydrides to new Co(II) complexes that were found to be active for the hydrogenation of terminal alkenes under catalytic hydrogenation conditions. An overall feature of the work described in this thesis is the formation of mononuclear cooperatively bound metal-substrate-boron complexes; chapter 5 provides fundamental guidelines for such substrate binding across a range of substrates. A key result uncovered here is that the 3-carbon tether for the appended borane displays ideal flexibility and mobility to 1) capture both inert and reactive substrates that bind with μ-1,1 and μ-1,2 binding modes and 2) switch between these modes. Collectively, the studies presented in this thesis demonstrate the important principles that appended borane Lewis acids can help stabilize reactive small molecules at transition metal centers that otherwise are unstable, and these intramolecular systems can regulate small molecule reactivity and facilitate novel reaction pathways.