1000141-63-8

Upstream product

• 1197-01-9 p-cymene-8-ol 
• 99-87-6 4-methylisopropylbenzene 

Downstream Products

• 6526-79-0 1-(4-methylphenyl)-1-methylethylamine 

Relevant academic research and scientific papers

Mangana(iii/iv)electro-catalyzed C(sp3)-H azidation

Manganaelectro-catalyzed azidation of otherwise inert C(sp3)-H bonds was accomplished using most user-friendly sodium azide as the nitrogen-source. The operationally simple, resource-economic C-H azidation strategy was characterized by mild reaction conditions, no directing group, traceless electrons as the sole redox-reagent, Earth-abundant manganese as the catalyst, high functional-group compatibility and high chemoselectivity, setting the stage for late-stage azidation of bioactive compounds. Detailed mechanistic studies by experiment, spectrophotometry and cyclic voltammetry provided strong support for metal-catalyzed aliphatic radical formation, along with subsequent azidyl radical transfer within a manganese(iii/iv) manifold.

Site-Selective Copper-Catalyzed Azidation of Benzylic C-H Bonds

Site selectivity represents a key challenge for non-directed C-H functionalization, even when the C-H bond is intrinsically reactive. Here, we report a copper-catalyzed method for benzylic C-H azidation of diverse molecules. Experimental and density functional theory studies suggest the benzyl radical reacts with a CuII-azide species via a radical-polar crossover pathway. Comparison of this method with other C-H azidation methods highlights its unique site selectivity, and conversions of the benzyl azide products into amine, triazole, tetrazole, and pyrrole functional groups highlight the broad utility of this method for target molecule synthesis and medicinal chemistry.

Manganese-Catalyzed Oxidative Azidation of C(sp3)-H Bonds under Electrophotocatalytic Conditions

The selective installation of azide groups into C(sp3)-H bonds is a priority research topic in organic synthesis, particularly in pharmaceutical discovery and late-stage diversification. Herein, we demonstrate a generalized manganese-catalyzed oxidative azidation methodology of C(sp3)-H bonds using nucleophilic NaN3 as an azide source under electrophotocatalytic conditions. This approach allows us to perform the reaction without the necessity of adding an excess of the substrate and successfully avoiding the use of stoichiometric chemical oxidants such as iodine(III) reagent or NFSI. A series of tertiary and secondary benzylic C(sp3)-H, aliphatic C(sp3)-H, and drug-molecule-based C(sp3)-H bonds in substrates are well tolerated under our protocol. The simultaneous gram-scale synthesis and the ease of transformation of azide to amine collectively advocate for the potential application in the preparative synthesis. Good reactivity of the tertiary benzylic C(sp3)-H bond and selectivity of the tertiary aliphatic C(sp3)-H bond in substrates to incorporate nitrogen-based functionality at the tertiary alkyl group also provide opportunities to manipulate numerous potential medicinal candidates. We anticipate our synthetic protocol, consisting of metal catalysis, electrochemistry, and photochemistry, would provide a new sustainable option to execute challenging organic synthetic transformations.

Benzylic C-H Azidation Using the Zhdankin Reagent and a Copper Photoredox Catalyst

An azidation method for C-N bond formation at benzylic C-H positions is described using copper-catalyzed visible light photochemistry and the Zhdankin azidoiodinane reagent. The method is applicable to a wide range of substrates bearing different functional groups and having a primary, secondary, or tertiary benzylic position, and is thought to proceed through a radical chain reaction.

Metal-catalysed azidation of tertiary C-H bonds suitable for late-stage functionalization

Many enzymes oxidize unactivated aliphatic C-H bonds selectively to form alcohols; however, biological systems do not possess enzymes that catalyse the analogous aminations of C-H bonds. The absence of such enzymes limits the discovery of potential medicinal candidates because nitrogen-containing groups are crucial to the biological activity of therapeutic agents and clinically useful natural products. In one prominent example illustrating the importance of incorporating nitrogen-based functionality, the conversion of the ketone of erythromycin to the -N(Me)CH2 - group in azithromycin leads to a compound that can be dosed once daily with a shorter treatment time. For such reasons, synthetic chemists have sought catalysts that directly convert C-H bonds to C-N bonds. Most currently used catalysts for C-H bond amination are ill suited to the intermolecular functionalization of complex molecules because they require excess substrate or directing groups, harsh reaction conditions, weak or acidic C-H bonds, or reagents containing specialized groups on the nitrogen atom. Among C-H bond amination reactions, those forming a C-N bond at a tertiary alkyl group would be particularly valuable, because this linkage is difficult to form from ketones or alcohols that might be created in a biosynthetic pathway by oxidation. Here we report a mild, selective, iron-catalysed azidation of tertiary C-H bonds that occurs without excess of the valuable substrate. The reaction tolerates aqueous environments and is suitable for the functionalization of complex structures in the late stages of a multistep synthesis. Moreover, this azidation makes it possible to install a range of nitrogen-based functional groups, including those from Huisgen 'click' cycloadditions and the Staudinger ligation. We anticipate that these reactions will create opportunities to modify natural products, their precursors and their derivatives to produce analogues that contain different polarity and charge as a result of nitrogen-containing groups. It could also be used to help identify targets of biologically active molecules by creating a point of attachment - for example, to fluorescent tags or 'handles' for affinity chromatography - directly on complex molecular structures.

Evidence for significant through-space and through-bond electronic coupling in the 1,4-diphenylcyclohexane-1,4-diyl radical cation gained by absorption spectroscopy and DFT calculations

Photoinduced single-electron-transfer promoted oxidation of 2,5-diphenyl-l,5-hexadiene by using N-methylquinolinium tetrafluoroborate/ biphenyl co-sensitization takes place with the formation of an intense electronic absorption band at 476 nm, which is attributed to the 1,4-diphenylcyclohexane-1,4-diyl radical cation. The absorption maximum (λob) of this transient occurs at a longer wavelength than is expected for either the cumyl radical or the cumyl cation components. Substitution at the para positions of the phenyl groups in this radical cation by CH3O, CH3, F, Cl, and Br leads to an increasingly larger redshift of λob. A comparison of the ρ value, which was obtained from a Hammett plot of the electronic transition energies of the radical cations versus σ+, with that for the cumyl cation shows that the substituent effects on the transition energies for the 1,4-diarylcyclohexane-1,4-diyl radical cations are approximately one half of the substituent effects on the transition energies of the cumyl cation. The observed substitu_ent-induced redshifts of λob and the reduced sensitivity of λob to substituent changes are in accordance with the proposal that significant through-space and -bond electronic interactions exist between the cumyl radical and the cumyl cation moieties of the 1,4-diphenylcyclohexane-1,4-diyl radical cation. This proposal gains strong support from the results of density functional theory (DFT) calculations. Moreover, the results of time-dependent DFT calculations indicate that the absorption band at 476 nm for the 1,4-diphenylcyclohexane-1,4-diyl radical cation corresponds to a SOMO-3-SOMO transition.