Discovery, Invention and Development of New Bond Forming Reactions using Light.
Abstract
Serendipitous discoveries have led to the development of powerful synthetic transformations now routinely employed by synthetic orga"nic chemists, however, manipulation of this paradigm as a practical approach to reaction discovery has been little explored. Recentl""y, our group discovered a previously elusive photoredoxcatalyzed C~H arylation protocol through an accelerated serendipity approach,"" demonstrating the potential of this strategy to reveal new chemical reactivity. In this research proposal, we aim to exploit and ac""celerate thephenomenon of serendipity to drive the development of novel, highly enabling methodologies and evaluate this reaction d"evelopment approach in the context of distinct mono- and dual-catalytic platforms. We envision that this can be accomplished through the synergistic merger of high-throughput experimentation and computational analysis. By employing high-throughput experimentation" techniques, thousands of reactions can be conducted inparallel to evaluate a wide range of traditionally ~non-reactive~ substrate"" combinations under various reaction conditions, allowing the rapid discovery of new reactivity. Initial hits from this high-through"put approach can then be explored further by using computational analysis to probe the feasibility of potential mechanistic pathways". This in silico mechanistic evaluation will serve as a guide for the rational design of new experiments, thereby streamlining furt"her reaction optimization and investigation. 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 outlined dual strategy towards synthetic methodology development will aim to address the broad range of highly challenging synthetic problems outlined in Aims 1-20. As" such, this research program will target the development of valuable chemical transformations including, but not limited to, alcohol"" C~O bond cleavage,catalytic deracemization, visible light photon upconversion, C~H functionalization, and C~C bond activation. I""mportantly, the realization of catalytic strategies that address the synthetic goals outlined in Aims 1-20 could facilitate the cons""truction of valuable molecular scaffolds, such as the synthesis of energy-dense small ring architectures via ring contraction, the d""esign 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
- Mar 26, 2018
- Source ID
- N000141812178
Entities
People
- David MacMillan
Organizations
- Office of Naval Research
- Trustees of Princeton University
- United States Navy