Amidins and Imidates as Transient Directing Groups in C-H-activating Reactions
Final Report Abstract
C-H activating reactions are important transformations for the efficient refinement of simple starting materials, especially aromatics. To carry out C-H activations efficiently, directing groups are needed to guide the C-H activating metal catalyst, such as Pd(II), to a specific C-H bond. In this project, amidines and imidates, which have been less explored as directing groups, were investigated. In contrast, these groups were intended to be attached transiently, through in situ formation, rather than permanently. Furthermore, as part of the "Scientists as Refugees" program, regioselective enantioselective transformations of a similar nature were studied. Contrary to initial assumptions, it was not possible to reversibly attach amidine and imidate protecting groups to phenols and anilines, even after various structural modifications of the substrates and directing groups. However, by the end of the project, it was demonstrated that amidines and imidates are efficient directing groups for palladiumcatalyzed C-H activating alkenylation. The resulting reaction products were used for the synthesis of heterocyclic systems, which are often found as structural motifs in biologically active compounds. The synthesis approach we developed is complementary to previously known methods for constructing these structural motifs. In an additional project, C-H activating reactions without the use of directing groups were developed. We achieved, for the first time, a stereoablative synthesis of chiral benzyl alcohols with very high regioselectivity and excellent enantioselectivity. Additionally, we successfully developed an oxidative spirocyclization and verified the structure of the in situ generated chiral iodane in situ. These structures were subsequently transformed into a range of valuable chiral building blocks.
Publications
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N-Heterocycle-Stabilized Hypervalent Iodine Compounds - Highly Modular Oxidation Catalysts with Unique Reactivities, Kyoto (Japan), 27th International Society of Chemistry Congress, 09/2019, Invited Lecture.
Boris J. Nachtsheim
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N-Heterocycle-Stabilized Hypervalent Iodine Compounds – From Synthesis to Applications, HALCHEM IX, Perugia (Italy) 09/2019, Invited Plenary Lecture.
Boris J. Nachtsheim
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An Enantioconvergent Benzylic Hydroxylation Using a Chiral Aryl Iodide in a Dual Activation Mode. ACS Catalysis, 10(15), 8042-8048.
Abazid, Ayham H.; Clamor, Nils & Nachtsheim, Boris J.
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Application of chiral triazole-substituted iodoarenes in the enantioselective construction of spirooxazolines. Chemical Communications, 57(70), 8822-8825.
Abazid, Ayham H. & Nachtsheim, Boris J.
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Application of Iodanes as Group Transfer Reagents, 09/2021 HALCHEM X, Lodcz (Polen), Poster Presentation
Nils Clamor
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Modern Iodane Chemistry – From New Reagents to Chiral Transformations, 02/21, Stockholm University(Sweden), Invited Zoom Lecture.
Boris J. Nachtsheim
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The Versatile Chemistry of N-Heterocycle-stabilized Iodanes (NHIs), 09/2021 HAL- CHEM X, Lodcz(Polen), Invited Lecture.
Boris J. Nachtsheim
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Structure Elucidation of In Situ Generated Chiral Hypervalent Iodine Complexes via Vibrational Circular Dichroism (VCD). Angewandte Chemie International Edition, 61(50).
Golub, Tino P.; Abazid, Ayham H.; Nachtsheim, Boris J. & Merten, Christian
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The Versatile Chemistry of N-Heterocycle-stabilized Iodanes (NHIs), 11/2022, EPFL Lausanne(Switzerland), Invited Lecture
Boris J. Nachtsheim
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The Versatile Chemistry of N-Heterocycle-stabilized Iodanes – From Synthesis to Halogen Bond Catalysis, 11/2022, ISXB5, Chiba (Japan), Invited Lecture.
Boris J. Nachtsheim
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The Versatile Chemistry of N-Heterocycle-stabilized Iodanes (NHIs), 06/2023 ICHIC7, Stockholm University, Oral Communication.
Boris J. Nachtsheim
