Liquid-handling Robot and UPLC-MS to Enable High-throughput Experimentation for Research on Chemical Reaction Development
Abstract
Serendipitous discoveries have led to the development of powerful synthetic transformations now routinely employed by synthetic organic chemists, however, manipulation of this paradigm as a practical approach to reaction discovery has been little explored. Recently, our group discovered a previously elusive photoredox-catalyzed C~H arylation protocol through an accelerated serendipity approach, demonstrating the potential of this strategy to reveal new chemical reactivity. In this proposal, a dedicated system for conducting high-throughput experimentation is proposed to facilitate further exploitation of accelerated serendipity in the context of chemical reaction development. By employing high throughput experimentation techniques, thousands of reactions can be conducted in parallel to evaluate a wide range of traditionally ~non-reactive~ substrate combinations under various reaction conditions, allowing the rapid discovery of new reactivity. In order to obtain such high reaction throughput, two critical pieces of equipment are requested in this proposal. First, a liquid-handling robot is desired to allow for rapid and efficient preparation of a large volume of chemical reactions. Second, instrumentation enabling ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) is requested to allow for expeditious reaction analysis. Initial hits from this high-throughput approach can then be explored further to develop useful synthetic methodologies. We anticipate that this powerful approach to reaction discovery and development will enable us to deliver novel solutions to key challenges within the field of organic chemistry. The proposed instrumentation will allow us to explore research in several areas of interest, including, but not limited to, alcohol C~O bond cleavage, selective protein conjugation, catalytic deracemization, C~C bond activation, and biomass depolymerization. Importantly, the realization of catalytic strategies that address the synthetic goals outlined in Aims 1-7 could facilitate the construction of valuable molecular scaffolds, such as the synthesis of energy-dense small ring architectures via ring contraction, the design of new functional materials through site-selective protein conjugation, and the generation of valuable chemical feedstocks via controlled depolymerization of abundant biopolymers.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 20, 2019
- Source ID
- N000141912536
Entities
People
- David MacMillan
Organizations
- Office of Naval Research
- Trustees of Princeton University
- United States Navy