The goal of the research proposed is to facilitate the construction of organic molecules by exploring unconventional reagents for cross-coupling and exploiting the unique attributes of such reagents. This will be accomplished by employing a recently developed, paradigm-shifting approach to cross-coupling involving a dual catalytic cycle. The two cycles, a photoredox catalytic cycle and a cross-coupling cycle, working in concert, will facilitate a single electron transmetalation protocol, allowing cross-coupling under mild conditions and, with the appropriate ligand, high levels of enantioselectivity via stereoconvergent transformations. In particular, methods to do so from inexpensive, bench-stable, commodity nonmetallic organic precursors will be sought. A process using such materials would be robust, cost-effective, and scalable, leading to a facile transition from the academic setting to a process development facility. Employing the dual catalytic systems that have proven effective in studies on the cross-coupling of organotrifluoroborates, the protocol will be extended to non-organometallic bulk source materials, namely hydrazines and sulfinate salts. Studies on these commodity materials will focus on practical methods of effecting radical formation under photoredox conditions and assessing their viability in being funneled into the base metal catalytic cycle. Organocatalysts and inexpensive inorganic materials will be explored as potential photocatalysts to enhance the sustainable profile of developed processes. Photoflow-based technologies and strategies will be examined as a means of enhancing scalability and effectivity. Diverse electrophilic coupling partners will be examined, and stereoconvergent processes will be developed to access enantioenriched alkyl substructures. This protocol will be transformative in enabling unprecedented C-C bond construction via cross-coupling from nonconventional, inexpensive coupling partners.
One of the workhorse reactions of drug discovery programs are cross-coupling reactions. While effective for accessing certain organic molecules, such methods are either impractical or impossible for accessing molecules containing important structural features. Moreover, they require costly starting materials with limited commercial availability. The proposed research outlines a method to use existing commodity chemicals as surrogates for traditional starting materials and utilizes a recently developed reaction pathway which circumvents the restrictions of classical cross-coupling reactions
| Cabrera-Afonso, María Jesús; Lu, Zhi-Peng; Kelly, Christopher B et al. (2018) Engaging sulfinate salts via Ni/photoredox dual catalysis enables facile Csp2 -SO2R coupling. Chem Sci 9:3186-3191 |
| Milligan, John A; Phelan, James P; Polites, Viktor C et al. (2018) Radical/Polar Annulation Reactions (RPARs) Enable the Modular Construction of Cyclopropanes. Org Lett 20:6840-6844 |
| Phelan, James P; Wiles, Rebecca J; Lang, Simon B et al. (2018) Rapid access to diverse, trifluoromethyl-substituted alkenes using complementary strategies. Chem Sci 9:3215-3220 |
| Phelan, James P; Lang, Simon B; Compton, Jordan S et al. (2018) Redox-Neutral Photocatalytic Cyclopropanation via Radical/Polar Crossover. J Am Chem Soc 140:8037-8047 |
| Lin, Kingson; Wiles, Rebecca J; Kelly, Christopher B et al. (2017) Haloselective Cross-Coupling via Ni/Photoredox Dual Catalysis. ACS Catal 7:5129-5133 |
| Patel, Niki R; Kelly, Christopher B; Siegenfeld, Allison P et al. (2017) Mild, Redox-Neutral Alkylation of Imines Enabled by an Organic Photocatalyst. ACS Catal 7:1766-1770 |
| Kelly, Christopher B; Patel, Niki R; Primer, David N et al. (2017) Preparation of visible-light-activated metal complexes and their use in photoredox/nickel dual catalysis. Nat Protoc 12:472-492 |
| Davies, Geraint H M; Mukhtar, Asma; Saeednia, Borna et al. (2017) Azaborininones: Synthesis and Structural Analysis of a Carbonyl-Containing Class of Azaborines. J Org Chem 82:5380-5390 |
| Remeur, Camille; Kelly, Christopher B; Patel, Niki R et al. (2017) Aminomethylation of Aryl Halides using ?-Silylamines Enabled by Ni/Photoredox Dual Catalysis. ACS Catal 7:6065-6069 |
| Lang, Simon B; Wiles, Rebecca J; Kelly, Christopher B et al. (2017) Photoredox Generation of Carbon-Centered Radicals Enables the Construction of 1,1-Difluoroalkene Carbonyl Mimics. Angew Chem Int Ed Engl 56:15073-15077 |
Showing the most recent 10 out of 14 publications
