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. 2024 Apr 3;146(13):8904-8914.
doi: 10.1021/jacs.3c11555. Epub 2024 Mar 20.

Catalyst and Medium Control over Rebound Pathways in Manganese-Catalyzed Methylenic C-H Bond Oxidation

Marco Galeotti  1 , Massimo Bietti  2 , Miquel Costas  1
Affiliations

Catalyst and Medium Control over Rebound Pathways in Manganese-Catalyzed Methylenic C-H Bond Oxidation

Marco Galeotti et al. J Am Chem Soc. .

Abstract

The C(sp3)-H bond oxygenation of a variety of cyclopropane containing hydrocarbons with hydrogen peroxide catalyzed by manganese complexes containing aminopyridine tetradentate ligands was carried out. Oxidations were performed in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and 2,2,2-trifluoroethanol (TFE) using different manganese catalysts and carboxylic acid co-ligands, where steric and electronic properties were systematically modified. Functionalization selectively occurs at the most activated C-H bonds that are α- to cyclopropane, providing access to carboxylate or 2,2,2-trifluoroethanolate transfer products, with no competition, in favorable cases, from the generally dominant hydroxylation reaction. The formation of mixtures of unrearranged and rearranged esters (oxidation in HFIP in the presence of a carboxylic acid) and ethers (oxidation in TFE) with full control over diastereoselectivity was observed, confirming the involvement of delocalized cationic intermediates in these transformations. Despite such a complex mechanistic scenario, by fine-tuning of catalyst and carboxylic acid sterics and electronics and leveraging on the relative contribution of cationic pathways to the reaction mechanism, control over product chemoselectivity could be systematically achieved. Taken together, the results reported herein provide powerful catalytic tools to rationally manipulate ligand transfer pathways in C-H oxidations of cyclopropane containing hydrocarbons, delivering novel products in good yields and, in some cases, outstanding selectivities, expanding the available toolbox for the development of synthetically useful C-H functionalization procedures.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Competitive Rebound Pathways in C–H Bond Oxidation Promoted by Enzymes and Bioinspired Catalysts (X = Halogen or Pseudohalogen)
Figure 1
Figure 1
State of the art for manganese-catalyzed C(sp3)–H oxidation via carboxylate rebound: (A) ref (9), (B) ref (15)a, and (C) ref (16).
Figure 2
Figure 2
Oxidation of ent-trachyloban-19-oate with H2O2 catalyzed by Mn(Ar–CF3pdp).
Scheme 2
Scheme 2. (A) Effect of Acetic Acid on the Oxidation of S1; (B) Proposed Mechanistic Pathways for Carboxylate and Hydroxyl Transfer in the Oxidation of S1
Pie charts refer to product selectivities while adjacent small circles to normalized product ratios.
Scheme 3
Scheme 3. Effect of Catalyst Structure on the Oxidation of S1
Pie charts refer to product selectivities while adjacent small circles to normalized product ratios.
Scheme 4
Scheme 4. Effect of the Carboxylic Acid (XnOH) on the Oxidation of S1,
Pie charts refer to product selectivities while adjacent small circles to normalized product ratios. Mn(TIPSpdp) 1 mol % and H2O2 3.0 equiv were used.
Scheme 5
Scheme 5. Steric and Electronic Effects on the Oxidation of S1
Pie charts refer to product selectivities while adjacent small circles to normalized product ratios.
Scheme 6
Scheme 6. Oxidation of S1 with H2O2 in 2,2,2-Trifluoroethanol (TFE) Catalyzed by Complexes 1–8, the Structures for Which Are Displayed in Scheme 3
Pie charts refer to product selectivities while adjacent small circles to normalized product ratios.
Scheme 7
Scheme 7. Oxidation of S3
Pie charts refer to product selectivities while adjacent small circles to normalized product ratios.
Scheme 8
Scheme 8. Oxidation of (A) S2 and (B) S3
The structures of the oxygenation products at C-5, C-6, and C-9 of S3 (sp = side products) are reported in Tables S6 and S7. Pie charts refer to product selectivities while adjacent small circles refer to normalized product ratios.
Scheme 9
Scheme 9. Summary of the Competitive Rebound Pathways Observed in the Oxidation of Substrates S1–S3 under Different Experimental Conditions
Reference (16).
See this image and copyright information in PMC

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