Trifluoromethyl Vinyl Sulfide: A Building Block for the Synthesis of CF<sub>3</sub>S-Containing Isoxazolidines

Riesco-Domínguez, Alejandra; Wiel, Jeroen van de; Hamlin, Trevor A.; Beek, Bas van; Lindell, Stephen D.; Blanco‐Ania, Daniel; Bickelhaupt, F. Matthias; Rutjes, Floris P. J. T.

doi:10.1021/acs.joc.7b02639

Cited by 22 publications

(15 citation statements)

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“…Therefore, the difference in reactivity is purely based on steric interactions (see Figure b) and could be traced back to closed shell interactions between the tert ‐butyl group of 9 and ADIBO* (see Supporting Information). We have previously found Δ E Pauli to be a decisive factor controlling the regioselectivity of 1,3‐dipolar cycloadditions and now identify this energy term to be responsible for the observed chemoselectivity of tertiary azides.…”

Section: Figurementioning

confidence: 64%

Chemoselectivity of Tertiary Azides in Strain‐Promoted Alkyne‐Azide Cycloadditions

Svatunek

Houszka

Hamlin

et al. 2018

Chemistry A European J

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The strain‐promoted alkyne‐azide cycloaddition (SPAAC) is the most commonly employed bioorthogonal reaction with applications in a broad range of fields. Over the years, several different cyclooctyne derivatives have been developed and investigated in regard to their reactivity in SPAAC reactions with azides. However, only a few studies examined the influence of structurally diverse azides on reaction kinetics. Herein, we report our investigations of the reactivity of primary, secondary, and tertiary azides with the cyclooctynes BCN and ADIBO applying experimental and computational methods. All azides show similar reaction rates with the sterically non‐demanding cyclooctyne BCN. However, due to the increased steric demand of the dibenzocyclooctyne ADIBO, the reactivity of tertiary azides drops by several orders of magnitude in comparison to primary and secondary azides. We show that this chemoselective behavior of tertiary azides can be exploited to achieve semiorthogonal dual‐labeling without the need for any catalyst using SPAAC exclusively.

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Section: Figurementioning

confidence: 64%

Chemoselectivity of Tertiary Azides in Strain‐Promoted Alkyne‐Azide Cycloadditions

Svatunek

Houszka

Hamlin

et al. 2018

Chemistry A European J

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“…This analysis can be applied to single geometries or multiple geometries along a scan or reaction coordinate, to provide information on the nature of interaction between the fragments and the potential energy surface. This method has been widely applied for a broad range of chemical systems such as cycloadditions, ene reactions, metal complexes and catalysis, organocatalysis, and addition and substitution reactions …”

Section: Introductionmentioning

confidence: 99%

autoDIAS: a python tool for an automated distortion/interaction activation strain analysis

Svatunek

Houk

2019

J Comput Chem

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The distortion/interaction activation strain (DIAS) analysis is a powerful tool for the investigation of energy barriers. However, setup and data analysis of such a calculation can be cumbersome and requires lengthy intervention of the user. We present autoDIAS, a python tool for the automated setup, performance, and data extraction of the DIAS analysis, including automated detection of fragments and relevant geometric parameters. © 2019 Wiley Periodicals, Inc.

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“…Diazo compounds have been proposed as agents for bioorthogonal cycloadditions, as they show orthogonality to commonly used azide cycloadditions and provide high reactivity . Nitrones have been found to be valuable building blocks for the preparation of potential antiviral agents and agrochemicals, while nitrile oxides have found the application in the preparation of nucleoside and nucleotide analogues and as bioorthogonal agents …”

Section: Introductionmentioning

confidence: 99%

Elucidating the Trends in Reactivity of Aza‐1,3‐Dipolar Cycloadditions

et al. 2018

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This report describes a density functional theory investigation into the reactivities of a series of aza‐1,3‐dipoles with ethylene at the BP86/TZ2P level. A benchmark study was carried out using QMflows, a newly developed program for automated workflows of quantum chemical calculations. In total, 24 1,3‐dipolar cycloaddition (1,3‐DCA) reactions were benchmarked using the highly accurate G3B3 method as a reference. We screened a number of exchange and correlation functionals, including PBE, OLYP, BP86, BLYP, both with and without explicit dispersion corrections, to assess their accuracies and to determine which of these computationally efficient functionals performed the best for calculating the energetics for cycloaddition reactions. The BP86/TZ2P method produced the smallest errors for the activation and reaction enthalpies. Then, to understand the factors controlling the reactivity in these reactions, seven archetypal aza‐1,3‐dipolar cycloadditions were investigated using the activation strain model and energy decomposition analysis. Our investigations highlight the fact that differences in activation barrier for these 1,3‐DCA reactions do not arise from differences in strain energy of the dipole, as previously proposed. Instead, relative reactivities originate from differences in interaction energy. Analysis of the 1,3‐dipole–dipolarophile interactions reveals the reactivity trends primarily result from differences in the extent of the primary orbital interactions.

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Trifluoromethyl Vinyl Sulfide: A Building Block for the Synthesis of CF₃S-Containing Isoxazolidines

Abstract: Trifluoromethyl vinyl sulfide, a potential building block for pharmaceutically and agrochemically relevant products, is prepared and used for the first time in high-pressure-mediated 1,3-dipolar cycloaddition reactions with nitrones to synthesize (trifluoromethyl)sulfanyl isoxazolidines.

Cited by 22 publications

References 50 publications

Chemoselectivity of Tertiary Azides in Strain‐Promoted Alkyne‐Azide Cycloadditions

Chemoselectivity of Tertiary Azides in Strain‐Promoted Alkyne‐Azide Cycloadditions

autoDIAS: a python tool for an automated distortion/interaction activation strain analysis

Elucidating the Trends in Reactivity of Aza‐1,3‐Dipolar Cycloadditions

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Trifluoromethyl Vinyl Sulfide: A Building Block for the Synthesis of CF3S-Containing Isoxazolidines

Abstract: Trifluoromethyl vinyl sulfide, a potential building block for pharmaceutically and agrochemically relevant products, is prepared and used for the first time in high-pressure-mediated 1,3-dipolar cycloaddition reactions with nitrones to synthesize (trifluoromethyl)sulfanyl isoxazolidines.

Cited by 22 publications

References 50 publications

Chemoselectivity of Tertiary Azides in Strain‐Promoted Alkyne‐Azide Cycloadditions

Chemoselectivity of Tertiary Azides in Strain‐Promoted Alkyne‐Azide Cycloadditions

autoDIAS: a python tool for an automated distortion/interaction activation strain analysis

Elucidating the Trends in Reactivity of Aza‐1,3‐Dipolar Cycloadditions

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Product

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Trifluoromethyl Vinyl Sulfide: A Building Block for the Synthesis of CF₃S-Containing Isoxazolidines