Research

We are a young research group that is applying “systems” and supramolecular ways of thinking to solve problems in catalysis as it relates to organic chemistry and the chemical origins of life. Interrelated areas of focus include:

1) Self-organized reaction networks to understand the origin of life

metabolism

How did life’s chemical pathways emerge before there were enzymes to act as catalysts? Why does biochemistry use the reactions and pathways that it does and not others? This ERC-funded project aims to understand  the prebiotic origins of biological metabolism. In the first phase of the project, we experimentally investigated the possibility that core biological anabolic pathways present in early life may have originated as non-enzymatic chemistry, including the acetyl CoA pathway [1] and the reverse Krebs cycle [2]. Now in the second phase of the project, we are exploring reaction networks that could have been precursors to catabolic cycles, such as the Krebs and glyoxylate cycles [3]. Our results suggest that biological metabolism was an outgrowth of geochemistry. For an overview, see below for Joseph’s short talk from the 2018 ACS meeting in Boston.

[1] Nature Ecol. Evol. 2018, 2, 1019-1024. [2] Nature Ecol. Evol. 2017, 1, 1716-1721. [3] Nature 2019, 569, 104-107.

2) Vibrational Strong Coupling for organic chemistry and catalysis

TOC graphic

This project aims to develop a completely new way to control the rate and selectivity of organic reactions: by selectively modifying relevant molecular vibrations by running the reaction between appropriately-spaced mirrors. Vibrational Strong Coupling (VSC) is an emerging field in the quantum optics community.  A collaboration between our group (organic chemistry) and the group of Prof. Thomas Ebbesen (a world leader in VSC), aims to exploit this phenomenon for use in organic synthesis and catalysis. Thus far, we have shown that VSC can be used to change the rates [1] and selectivities [2] of ground state organic reactions. Ongoing work aims to use VSC to understand which functional groups and reaction mechanisms are most susceptible to VSC, as well as to explore the effect of VSC on catalysis.

[1] Angew. Chem. Int. Ed. 2016, 55, 11462. [2] Science 2019, 363, 615.

3) Aggregation in Brønsted acid catalysis

We have uncovered some interesting solvent effects that push the boundaries of known reactivity of Brønsted acid catalysis. Mechanistic experiments suggest that the formation of higher order aggregates involving solvents such as nitromethane and hexafluoroisopropanol are critical to the observed reactivity. We are working to deepen our understanding of these phenomena and continue to exploit them to develop methods of interest for organic synthesis, such as the direct nucleophilic substitution of alcohols [1][2] or alkyl fluorides [3] and the ring opening of cyclopropanes [4].

[1] (a) Angew. Chem. Int. Ed. 2017, 56, 3085. (b)  J. Am. Chem. Soc. 2015, 137, 9555. (c) Org. Biomol. Chem. 2014, 12, 5990. [2] For our review of catalytic dehydrative alcohol substitution, see Synthesis 2016, 48, 935. [3] (a) ACS Catalysis 2016, 6, 3670. (b)  J. Fluor. Chem. 2017, 193, 45. [4] (a) Org. Lett. 2018, 20, 574. (b) Chem. Sci. 20189, 6411.

4) Catalyst discovery using complex mixtures – a systems approach

toc-synpacts

We have developed a simple algorithmic approach for screening and deconvoluting complex mixtures of catalyst components with the goal of rapidly identifying new catalysts and cooperative effects.[1] We have used this strategy to uncover new organoboron [2] and nickel [2][3] catalysts, and have found that catalysts selected in this way tend to be useful in multicatalysis.[4] The continuing goal of this project is to discover new  cooperative effects and multicatalytic processes.

[1] For an account of our recent work in this area, see: Synlett 2016, 27, 2637. [2] Chem. Sci. 2015, 6, 2501. [3] J. Org. Chem. 2015, 80, 6922. [4] Chem. Eur. J. 2016, 22, 12274.

For more information on ongoing projects, please contact Dr. Moran directly.