Enantioselective Oxidative Phenol Coupling by Chiral Multicoordinated Iron Complexes


חדר הסמינרים


Prof. Doron Pappo Department of Chemistry, Ben-Gurion University of the Negev

Enantioselective Oxidative Phenol Coupling by Chiral Multicoordinated Iron Complexes
Abstract: Enantioselective oxidative coupling reactions offer a powerful strategy for preparing optical pure biaryl compounds that serve as building blocks, ligands, and catalysts in asymmetric transformations.1 The regio-, chemo-, and enantioselectivity in these processes are determined during the C−C bond formation step.1 Thus, preparing chiral redox iron complexes that catalyze oxidative coupling reactions with face selection is a challenging task, rarely being achieved.
FeCl3 is a highly effective and selective multi-coordinated catalyst for the oxidative coupling between two phenols or between phenols and 2-aminonaphthalenes. Inducing asymmetry to this catalyst by attaching chiral chelators limits the number of free coordination sites, causing mechanistic alternations that affect the reactivity and selectivity. Therefore, multi-coordinated iron complexes with chiral counter-anions were prepared to induce asymmetry into FeCl3-catalyzed transformations without affecting the chemoselectivity.
In this talk, we will describe catalytic conditions based on FeCl3 for the oxidative cross-coupling between substituted phenols,2,3 including 2-naphthols and 2-aminonaphthalene derivatives.4 A series of initial-rate kinetic experiments that provided the basis for a mechanistic understanding,5 and for the invention of [Fe(phosphate)3] and [Fe((Ra)-BINSate)]+ (BINSate = 1,1’-Binaphthalene-2,2’-disulfonate) complexes. [Fe(phosphate)3] catalyzes the oxidative coupling of 2-naphthols, affording C1- and C2-symmetric 1,1’-bi-2-naphthols (BINOLs) in high efficiency and enantioselectivity (up to 88% yield and 94:6 er).6 While [Fe((Ra)-BINSate)]+ complexes effectively promotes the atroposelective oxidative cross-coupling between 2-naphthols and 2-aminonaphthalene derivatives, offering for the first time a general and straightforward entry to optically enriched 2‑Amino-2′-hydroxy-1,1′-binaphthyls [(Ra)-NOBINs] with exceptional yields and enantioselective ratios (up to 99% yield and 96:4 er).7
1. Shalit, H.; Dyadyuk, A.; Pappo, D., Selective Oxidative Phenol Coupling by Iron Catalysis. J. Org. Chem. 2019, 84 (4), 1677-1686.
2. Libman, A.; Shalit, H.; Vainer, Y.; Narute, S.; Kozuch, S.; Pappo, D., Synthetic and Predictive Approach to Unsymmetrical Biphenols by Iron-Catalyzed Chelated Radical-Anion Oxidative Coupling. J. Am. Chem. Soc. 2015, 137 (35), 11453-11460.
3. Gaster, E.; Vainer, Y.; Regev, A.; Narute, S.; Sudheendran, K.; Werbeloff, A.; Shalit, H.; Pappo, D., Significant Enhancement in the Efficiency and Selectivity of Iron-Catalyzed Oxidative Cross-Coupling of Phenols by Fluoroalcohols. Angew. Chem. Int. Ed. 2015, 54 (14), 4198-4202.
4. Forkosh, H.; Vershinin, V.; Reiss, H.; Pappo, D., Stereoselective Synthesis of Optically Pure 2-Amino-2′-hydroxy-1,1′-binaphthyls. Org. Lett. 2018, 20 (8), 2459-2463.
5. Vershinin, V.; Forkosh, H.; Ben-Lulu, M.; Libman, A.; Pappo, D., Mechanistic Insights into the FeCl3-Catalyzed Oxidative Cross-Coupling of Phenols with 2-Aminonaphthalenes. J. Org. Chem. 2021, 86 (1), 79-90.
6. Narute, S.; Parnes, R.; Toste, F. D.; Pappo, D., Enantioselective Oxidative Homocoupling and Cross-Coupling of 2-Naphthols Catalyzed by Chiral Iron Phosphate Complexes. J. Am. Chem. Soc. 2016, 138 (50), 16553-16560.
7. Dyadyuk, A.; Vershinin, V.; Shalit, H.; Shalev, H.; More, N. Y.; Pappo, D., A Chiral Iron Disulfonate Catalyst for the Enantioselective Synthesis of 2-Amino-2′-hydroxy-1,1′-binaphthyls (NOBINs). J. Am. Chem. Soc. 2022, 144 (8), 3676-3684.