Regio- and chemoselective intermolecular primary C−H oxidation catalyzed by bioinspired manganese catalyst Siu-Chung Chan , Miquel Costas Universitat de Girona, Spain Email: baggiocsc3work@gmail.com Selective C( sp 3 )−H functionalization is a continuous quest for synthetic chemists as it represents a step- and atom-economic approach to diversify and construct complex molecules. Development of bioinspired manganese and iron catalysts in C( sp 3 )−H oxygenation under mild conditions has led to tremendous growth in this area, relies on the formation of high valent metal-oxo species as electrophilic hydrogen atom transfer (HAT) reagent for generation of carbon-centred radicals. 1, 2 However, site-selective oxidation of these ubiquitous aliphatic C−H bonds in organic molecules is still regarded as a challenging task. From thermodynamical point of view, the reactivity trend operated by HAT is greatly affected by bond dissociation energy (BDE) of the C−H bonds, so it prefers oxidation in the order of tertiary>secondary>>primary C−H sites and intermolecular oxidation of primary C−H bonds via HAT/rebound mechanism only reaches very limited success due to their high BDE. Conversely, polar effect operated at transition-state level of these radical reactions has been reported to play an important role for the site-selectivity control. 3 Indeed, fluorinated alcohols as hydrogen bond donor solvents promote remote C−H oxidation to stabilize the charge separation dipolar transition-state for the molecules that contain polar hydrogen bond accepting functional groups, thus amenable for overriding the reactivity trend from BDE of the C−H bonds. 4 Herein, we present our work of intermolecular primary C−H oxidation catalysed by manganese complexes in fluorinated alcohols. The medium effect of the solvents plays dual function for selective primary C−H oxidation in both thermodynamic and kinetic control: 1) The acidity of fluorinated alcohols enhances the electrophilicity of the high valent Mn-oxo to perform HAT from highly inert primary C−H bonds; 2) Strong hydrogen bond donating nature of fluorinated alcohols promotes remote primary C−H oxidation by introducing different polar functional groups as hydrogen bond acceptors in the molecules. Within this catalytic framework, we carried out detailed studies for fine tuning of the electronic properties of the catalysts, choice of solvents and their medium effects on the reactivity, distal electronic effect of different polar functional groups, torsional effect on cyclic substrates, and finally have developed the optimized experimental conditions for obtaining both high regio- and chemo-selective primary C−H oxidation products in satisfactory yield. References 1. M. C. Chen and C. White, Science , 2007, 318 , 783-787 2. L. Vicens, G, Olivo and M. Costas, ACS Catal., 2020, 10 , 8611-8631 3. A. Ruffoni, R. C. Mykura, M. Bietti and D. Leonori, Nat. Synth. , 2022, 1 , 682-695. 4. V. Dantignana, M. Milan, O. Cussó, A. Company, M. Bietti and M. Costas, ACS Cent. Sci. , 2017, 3 , 1350-1358.
P16F
© The Author(s), 2023
Made with FlippingBook Learn more on our blog