NOHCs - 3-Alkoxyimidazolylidenes (NOHCs): A new class of highly nucleophilic carbenes. Preparation, structural and reactivity studies, and new applications in asymmetric catalysis
Final Report Abstract
During this project we demonstrated the heterocyclization of α-hydroxyiminoketones and formaldimines to imidazole 3-oxides without a substituent at the 2-position, including the use of N-(adamantyloxy)formaldimine as starting material to obtain 1-(adamantyloxy)imidazole-3-oxides in high yields. O-Alkylation provides access to the corresponding 1,3-dialkoxyimidazolium salts in high yields. The corresponding symmetric 1,3-di(adamantyloxy)imidazolium salts were obtained through the reaction of adamantyloxyamine with glyoxal, formaldehyde, and hydrobromic acid. First indirect evidence for the corresponding NOHCs comes from the deprotonation and trapping of the intermediate imidazol-2-ylidenes with elemental sulfur. The same procedure was applied to optically active functionalized primary amines, thereby providing access in situ generated chiral NOHCs. The multistep synthesis of the optically active imidazole-2-thiones as trapping products of the intermediate carbenes occurs with preservation of the stereochemistry. Finally, we succeeded in synthesizing and characterizing the new class of free N- alkoxyheterocyclic (NOHC) carbenes from these 1,3-dialkoxyimidazolium salts. The NOHCs have remarkable electronic properties different from comparable NHCs. For instance, we demonstrate that an Arduengo-carbene analog displays the most upfield 13C NMR shift of any imidazolylidene. Evidence for the preparation of such carbenes also comes from an isolatable and crystalline NOHC-Au(I) chloride complex that follows the NMR shift trend as the carbene carbon signal in the Au(I)-complex is shifted upfield from similar imidazolylidene-Au(I) complexes. The 77Se and 15N NMR spectra were meticulously analyzed for a series of NOHC-selenium adducts demonstrating the contribution of the N–O-linkage to the electronic structure of the NOHCs. Remarkably, the 77Se NMR chemical shift of the 4,5-dimethyl-substituted NOHC is the highest reported to date for an imidazolylidene Se adduct, pointing to a very high πacidity of the carbene carbon. These properties are likely to make NOHCs attractive for applications as ligands and catalysts that will be explored next. What we have not accomplished is the application of the NOHCs to catalytic organic reactions. This is simply due to the significantly longer time we spent on characterizing the key NOHCs to the best of our abilities. We found this worthwhile to determine the course of action for applying this new compound class to selected organocatalytic reactions. As the results from these characterization studies are highly promising, we will pick up on this at a later stage. As anticipated, the combination of synthetic ability and physico-organic characterization provided a powerful approach to characterize a new class of molecules, the NOHCs. Computational chemistry methods were used to compute the electronic and structural properties and to compare them to the synthetic and physico-chemical results.
Publications
- 2-Unsubstituted Imidazole N-Oxides as Novel Precursors of Chiral 3-Alkoxyimidazol-2-ylidenes Derived from trans-1,2-Diaminocyclohexane and Other Chiral Amino Compounds. Molecules 2019, 24, 4398–4416
Grzegorz Mlostoń, Małgorzata Celeda, Marcin Jasinski, Katrzyna Urbaniak, Przemysław Boratyński, Peter R. Schreiner, Heinz Heimgartner
(See online at https://doi.org/10.3390/molecules24234398) - Synthesis and Selected Transformations of 2-Unsubstituted 1-(Adamantyloxy)imidazole 3-Oxides. Beilstein J. Org. Chem. 2019, 15, 497–505
Grzegorz Mlostoń, Małgorzata Celeda, Katarzyna Urbaniak, Vladyslav Bakhonskyi, Peter R. Schreiner, and Heinz Heimgartner
(See online at https://doi.org/10.3762/bjoc.15.43) - N-Alkoxyimidazolylidines (NOHCs): A new class of highly nucleophilic carbenes. Chem. Commun. 2022, 58, 1538–1541
Vladyslav V. Bakhonsky, Jonathan Becker, Grzegorz Mlostoń, and Peter R. Schreiner
(See online at https://doi.org/10.1039/D1CC05696D)
