Sletten, E. M., Nakamura, H., Jewett, J. C., & Bertozzi, C. R. (2010). Difluorobenzocyclooctyne: Synthesis, reactivity, and stabilization by β-cyclodextrin. Journal of the American Chemical Society, 132(33), 11799-11805.
PMID: 20666466;PMCID: PMC2923465;Abstract:
Highly reactive cyclooctynes have been sought as substrates for Cu-free cycloaddition reactions with azides in biological systems. To elevate the reactivities of cyclooctynes, two strategies, LUMO lowering through propargylic fluorination and strain enhancement through fused aryl rings, have been explored. Here we report the facile synthesis of a difluorobenzocyclooctyne (DIFBO) that combines these modifications. DIFBO was so reactive that it spontaneously trimerized to form two asymmetric products that we characterized by X-ray crystallography. However, we were able to trap DIFBO by forming a stable inclusion complex with β-cyclodextrin in aqueous media. This complex could be stored as a lyophilized powder and then dissociated in organic solvents to produce free DIFBO for in situ kinetic and spectroscopic analysis. Using this procedure, we found that the rate constant for the cycloaddition reaction of DIFBO with an azide exceeds those for difluorinated cyclooctyne (DIFO) and dibenzocyclooctyne (DIBO). Cyclodextrin complexation is therefore a promising approach for stabilizing compounds that possess the high intrinsic reactivities desired for Cu-free click chemistry. © 2010 American Chemical Society.
Cornali, B. M., Kimani, F. W., & Jewett, J. C. (2016). Cu-Click Compatible Triazabutadienes To Expand the Scope of Aryl Diazonium Ion Chemistry. Organic letters, 18(19), 4948-4950.
Triazabutadienes can be used to readily generate reactive aryl diazonium ions under mild, physiologically relevant conditions. These conditions are compatible with a range of functionalities that do not tolerate traditional aryl diazonium ion generation. To increase the utility of this aryl diazonium ion releasing chemistry an alkyne-containing triazabutadiene was synthesized. The copper-catalyzed azide-alkyne cycloaddition ("Cu-click") reaction was utilized to modify the alkyne-containing triazabutadiene and shown to be compatible with the nitrogen-rich triazabutadiene. One of the triazole products was tethered to a fluorophore, thus enabling the direct fluorescent labeling of a model protein.
Gálvez, E., Romea, P., Urpí, F., Jewett, J. C., & Rawal, V. H. (2009). Preparation of (S)-4-Isopropyl-N-propanoyl-1,3-thiazolidine-2-thione. Organic Syntheses, 86, 70-80.
Martinez-Ariza, G., Mehari, B. T., Pinho, L., Foley, C., Day, K., Jewett, J. C., & Hulme, C. (2017). Synthesis of fluorescent heterocycles via a Knoevenagel/[4+1]-cycloaddition cascade using acetyl cyanide. ORGANIC & BIOMOLECULAR CHEMISTRY, 15(29), 6076-6079.
Jewett, J. C., & Rawal, V. H. (2007). Total synthesis of pederin. Angewandte Chemie - International Edition, 46(34), 6502-6504.
PMID: 17645272;Abstract:
(Chemical Equation Presented) Blisteringly fast: The potent cytotoxic blistering agent pederin has been synthesized (see scheme). The synthesis is diastereoselective and concise (just 12 steps for the longest linear sequence), and features a formal hetero-Diels-Alder reaction of a hindered diene, a Mukaiyama-Michael reaction to set two additional stereocenters, and a Curtius rearrangement to stereospecifically introduce the aminal functionality. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.
