Research in the Jamison Group

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Continuous-Flow Chemistry

   As a contributing research group in the Novartis-MIT Center for Continuous Manufacturing, the Jamison Research Group seeks to develop chemical methods under continuous-flow conditions, which: (a) improve reaction efficiency (yield/selectivity); (b) decrease safety risks to researchers; (c) streamline multistep processes; and/or (d) realize chemical transformations that would otherwise be difficult or improbable.

   The DIBAL-H reduction of an ester to an aldehyde is notoriously plagued by difficulties with selectivity, often yielding a mixture of the starting ester, desired aldehyde and undesired over-reduced alcohol products. Executing this reaction using continuous flow conditions, however, not only drastically improves product selectivity (relative to batch conditions) but also, in some cases, reduces the reaction times to the millisecond time frame.

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   Continuous-flow chemistry has also allowed for new catalytic reaction systems to be developed. For example, we have found that continuous-flow photochemical generation of [CpRu]+ could be achieved from CpRu(ƞ6-C6H6); this new catalytic system was effective for ene-yne coupling reactions while enabling full recovery of the catalyst precursor. This innovation revealed new catalyst development opportunities and represents one of the first metal-mediated photochemical reactions under continuous-flow conditions.

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   The Jamison group is also interested in the development of one-flow multi-step processes. In one example, a Brønsted acid-catalyzed glycosylation followed by deprotection was developed. By telescoping the glycosylation and deprotection, the need for intermediate purification was circumvented thereby streamlining the synthesis of nucleosides.

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Representative Publications:
  • Zhang, Y., Blackman; M. L.; Leduc, A. B.; Jamison, T. F. "Peptide Fragment Coupling Using a Continuous-Flow Photochemical Rearrangement of Nitrones" Angew. Chem. Int. Ed. 2013. Download PDF
  • Kleinke, A; Jamison, T. F. “Hydrogen Free Alkene Reduction in Continuous Flow” Org. Lett. 2013, 15, 710-713. Download PDF
  • Shen, B.; Jamison, T. F. "Rapid Continuous Synthesis of 5′-Deoxyribonucleosides in Flow via Brønsted Acid Catalyzed Glycosylation" Org. Lett. 2012, 14, 3348-3351. Download PDF
  • Webb, D.; Jamison, T. F. "A Continuous Homologation of Esters: An Efficient Telescoped Reduction–Olefination Sequence" Org. Lett. 2012, 14, 2465-2467. Download PDF
  • Tucker, J. W.; Zhang, Y.; Jamison, T. F.; Stephenson, C. R. J. "Visible-Light Photoredox Catalysis in Flow" Angew. Chem., Int. Ed. 2012, 51, 4144-4147. Download PDF
  • Webb D.; Jamison, T. F. "Diisobutylaluminum Hydride Reductions Revitalized: A Fast, Robust, and Selective Continuous Flow System for Aldehyde Synthesis" Org. Lett. 2012, 14, 568-571. Download PDF
  • Gutierrez, A. C.; Jamison, T. F. “Continuous Photochemical Generation of Catalytically Active [CpRu]+ Complexes from CpRu(η6-C6H6)PF6” Org. Lett. 2011, 13, 6414-6417. Download PDF
  • Leduc, A. B.; Jamison, T. F. “Continuous Flow Oxidation of Alcohols and Aldehydes Utilizing Bleach and Catalytic Tetrabutylammonium Bromide” Org. Proc. Res. Dev. 2011, in press. Download PDF
  • Palde, P. B; Jamison, T. F. “Safe and Efficient Tetrazole Synthesis in a Continuous-Flow Microreactor” Angew. Chem., Int. Ed. 2011, 50, 3525-3528. Download PDF
  • Zaborenko, N.; Bedore, M. W.; Jamison, T. F.; Jensen, K. F. “Kinetic and Scale-Up Investigations of Epoxide Aminolysis in Microreactors at High Temperatures and Pressures” Org. Process Res. Dev. 2011, 15, 131-139. Download PDF