Titanocene-Catalyzed Hydrosilylation of Cyclic Ethers to Stereochemically Enriched Anti-Markovnikov Alcohols and Fatty Alcohols
Titanocene-Catalyzed Hydrosilylation of Cyclic Ethers to Stereochemically Enriched Anti-Markovnikov Alcohols and Fatty Alcohols
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DissertationPrüfungsdatum
20.05.2026Datum der Veröffentlichung
19.06.2026Erstgutachter
Gansäuer, AndreasZweitgutachter
Höger, SigurdMetadaten
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In this thesis, titanocene-catalyzed hydrosilylations are investigated as tools towards pharmaceutically relevant motifs. First, this work establishes a straightforward approach to stereochemically enriched anti-Markovnikov alcohols from a diastereomeric mixture of trisubstituted olefins via enantioselective epoxidation followed by the diastereoconverging Ti-catalyzed hydrosilylation. Central to this strategy is the use of a suitable enantioselective epoxidation method. In this context, the Shi-epoxidation fulfilled all requirements. It controls the absolute configuration of the less-substituted stereocenter regardless of the olefin's geometry. Moreover, it transforms both olefin isomers into their respective epoxides with high enantioselectivity. The subsequent titanocene-catalyzed hydrosilylation erases the stereochemical information at the higher-substituted carbon and establishes a new relative configuration with respect to the less-substituted stereocenter, resulting in a single stereoisomer of the desired anti-Markovnikov alcohol.
Second, this work focuses on optimizing the regioselectivity for the titanocene-catalyzed hydrosilylation of monosubstituted alkyl epoxides. The relatively slow radical opening of these substrates by Cp2Ti(III)H allows the hydricity of the active species to promote a competing nucleophilic pathway, yielding unwanted Markovnikov alcohols. To suppress this nucleophilic mechanism, the hydricity of the active species is reduced by modifying the cyclopentadienyl ligands of titanocene dichloride with strongly Lewis-acidic silyl groups, which intramolecularly coordinate to the titanium-bound hydride. By additionally using 1,4-dioxane as a cosolvent to precipitate Lewis-acidic Mg salts, the regioselectivity of epoxide opening is improved from a regioisomeric ratio of 63:37 to 93:7.
Finally, in this work, the titanocene-catalyzed hydrosilylation was applied to oxetanes. In contrast to the previous approach using Cp2Ti(III)Cl as the active species and an external HAT reagent, the hydrosilylation system efficiently reduces oxetanes towards the anti-Markovnikov alcohols without the formation of an elimination side product. The β-hydride elimination is avoided due to the fast intramolecular HAT step. Moreover, the higher stability of oxetanes suppresses the competing nucleophilic side reaction observed for the opening of monosubstituted epoxides. Therefore, no elaborate catalyst design is necessary to achieve high regioselectivity in the opening of monosubstituted alkyl oxetanes. The regioselectivity (r.r. 99:1) is even higher compared to the corresponding optimized epoxide opening reaction (r.r. 93:7) due to the stronger contact of the catalyst's ligands with the substrate in the transition state of oxetane opening.
Second, this work focuses on optimizing the regioselectivity for the titanocene-catalyzed hydrosilylation of monosubstituted alkyl epoxides. The relatively slow radical opening of these substrates by Cp2Ti(III)H allows the hydricity of the active species to promote a competing nucleophilic pathway, yielding unwanted Markovnikov alcohols. To suppress this nucleophilic mechanism, the hydricity of the active species is reduced by modifying the cyclopentadienyl ligands of titanocene dichloride with strongly Lewis-acidic silyl groups, which intramolecularly coordinate to the titanium-bound hydride. By additionally using 1,4-dioxane as a cosolvent to precipitate Lewis-acidic Mg salts, the regioselectivity of epoxide opening is improved from a regioisomeric ratio of 63:37 to 93:7.
Finally, in this work, the titanocene-catalyzed hydrosilylation was applied to oxetanes. In contrast to the previous approach using Cp2Ti(III)Cl as the active species and an external HAT reagent, the hydrosilylation system efficiently reduces oxetanes towards the anti-Markovnikov alcohols without the formation of an elimination side product. The β-hydride elimination is avoided due to the fast intramolecular HAT step. Moreover, the higher stability of oxetanes suppresses the competing nucleophilic side reaction observed for the opening of monosubstituted epoxides. Therefore, no elaborate catalyst design is necessary to achieve high regioselectivity in the opening of monosubstituted alkyl oxetanes. The regioselectivity (r.r. 99:1) is even higher compared to the corresponding optimized epoxide opening reaction (r.r. 93:7) due to the stronger contact of the catalyst's ligands with the substrate in the transition state of oxetane opening.
Schlagwörter
Katalyse, Radikale, Epoxide, Oxetane, Hydrosilylierung, Catalysis, Radicals, Epoxides, Oxetanes, Hydrosilylation
Klassifikation (DDC)
540 ChemieZugehörige Publikation(en)
https://doi.org/10.1002/chem.202301031https://doi.org/10.1002/chem.202402694
https://doi.org/10.1021/acscatal.5c08083
Goli, Harie: Titanocene-Catalyzed Hydrosilylation of Cyclic Ethers to Stereochemically Enriched Anti-Markovnikov Alcohols and Fatty Alcohols. - Bonn, 2026. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5-90212
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5-90212
@phdthesis{handle:20.500.11811/14224,
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5-90212,
author = {{Harie Goli}},
title = {Titanocene-Catalyzed Hydrosilylation of Cyclic Ethers to Stereochemically Enriched Anti-Markovnikov Alcohols and Fatty Alcohols},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2026,
month = jun,
note = {In this thesis, titanocene-catalyzed hydrosilylations are investigated as tools towards pharmaceutically relevant motifs. First, this work establishes a straightforward approach to stereochemically enriched anti-Markovnikov alcohols from a diastereomeric mixture of trisubstituted olefins via enantioselective epoxidation followed by the diastereoconverging Ti-catalyzed hydrosilylation. Central to this strategy is the use of a suitable enantioselective epoxidation method. In this context, the Shi-epoxidation fulfilled all requirements. It controls the absolute configuration of the less-substituted stereocenter regardless of the olefin's geometry. Moreover, it transforms both olefin isomers into their respective epoxides with high enantioselectivity. The subsequent titanocene-catalyzed hydrosilylation erases the stereochemical information at the higher-substituted carbon and establishes a new relative configuration with respect to the less-substituted stereocenter, resulting in a single stereoisomer of the desired anti-Markovnikov alcohol.
Second, this work focuses on optimizing the regioselectivity for the titanocene-catalyzed hydrosilylation of monosubstituted alkyl epoxides. The relatively slow radical opening of these substrates by Cp2Ti(III)H allows the hydricity of the active species to promote a competing nucleophilic pathway, yielding unwanted Markovnikov alcohols. To suppress this nucleophilic mechanism, the hydricity of the active species is reduced by modifying the cyclopentadienyl ligands of titanocene dichloride with strongly Lewis-acidic silyl groups, which intramolecularly coordinate to the titanium-bound hydride. By additionally using 1,4-dioxane as a cosolvent to precipitate Lewis-acidic Mg salts, the regioselectivity of epoxide opening is improved from a regioisomeric ratio of 63:37 to 93:7.
Finally, in this work, the titanocene-catalyzed hydrosilylation was applied to oxetanes. In contrast to the previous approach using Cp2Ti(III)Cl as the active species and an external HAT reagent, the hydrosilylation system efficiently reduces oxetanes towards the anti-Markovnikov alcohols without the formation of an elimination side product. The β-hydride elimination is avoided due to the fast intramolecular HAT step. Moreover, the higher stability of oxetanes suppresses the competing nucleophilic side reaction observed for the opening of monosubstituted epoxides. Therefore, no elaborate catalyst design is necessary to achieve high regioselectivity in the opening of monosubstituted alkyl oxetanes. The regioselectivity (r.r. 99:1) is even higher compared to the corresponding optimized epoxide opening reaction (r.r. 93:7) due to the stronger contact of the catalyst's ligands with the substrate in the transition state of oxetane opening.},
url = {https://hdl.handle.net/20.500.11811/14224}
}
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5-90212,
author = {{Harie Goli}},
title = {Titanocene-Catalyzed Hydrosilylation of Cyclic Ethers to Stereochemically Enriched Anti-Markovnikov Alcohols and Fatty Alcohols},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2026,
month = jun,
note = {In this thesis, titanocene-catalyzed hydrosilylations are investigated as tools towards pharmaceutically relevant motifs. First, this work establishes a straightforward approach to stereochemically enriched anti-Markovnikov alcohols from a diastereomeric mixture of trisubstituted olefins via enantioselective epoxidation followed by the diastereoconverging Ti-catalyzed hydrosilylation. Central to this strategy is the use of a suitable enantioselective epoxidation method. In this context, the Shi-epoxidation fulfilled all requirements. It controls the absolute configuration of the less-substituted stereocenter regardless of the olefin's geometry. Moreover, it transforms both olefin isomers into their respective epoxides with high enantioselectivity. The subsequent titanocene-catalyzed hydrosilylation erases the stereochemical information at the higher-substituted carbon and establishes a new relative configuration with respect to the less-substituted stereocenter, resulting in a single stereoisomer of the desired anti-Markovnikov alcohol.
Second, this work focuses on optimizing the regioselectivity for the titanocene-catalyzed hydrosilylation of monosubstituted alkyl epoxides. The relatively slow radical opening of these substrates by Cp2Ti(III)H allows the hydricity of the active species to promote a competing nucleophilic pathway, yielding unwanted Markovnikov alcohols. To suppress this nucleophilic mechanism, the hydricity of the active species is reduced by modifying the cyclopentadienyl ligands of titanocene dichloride with strongly Lewis-acidic silyl groups, which intramolecularly coordinate to the titanium-bound hydride. By additionally using 1,4-dioxane as a cosolvent to precipitate Lewis-acidic Mg salts, the regioselectivity of epoxide opening is improved from a regioisomeric ratio of 63:37 to 93:7.
Finally, in this work, the titanocene-catalyzed hydrosilylation was applied to oxetanes. In contrast to the previous approach using Cp2Ti(III)Cl as the active species and an external HAT reagent, the hydrosilylation system efficiently reduces oxetanes towards the anti-Markovnikov alcohols without the formation of an elimination side product. The β-hydride elimination is avoided due to the fast intramolecular HAT step. Moreover, the higher stability of oxetanes suppresses the competing nucleophilic side reaction observed for the opening of monosubstituted epoxides. Therefore, no elaborate catalyst design is necessary to achieve high regioselectivity in the opening of monosubstituted alkyl oxetanes. The regioselectivity (r.r. 99:1) is even higher compared to the corresponding optimized epoxide opening reaction (r.r. 93:7) due to the stronger contact of the catalyst's ligands with the substrate in the transition state of oxetane opening.},
url = {https://hdl.handle.net/20.500.11811/14224}
}
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