a Alkane (0.58 mmol, 1 equiv), DIB (2.03 mmol, 653 mg, 3.5 equiv), NaCl (1.74 mmol, 101 mg, 3.0 equiv) or KBr (0.75 mmol, 89 mg, 1.3 equiv), H2O (0.5 mL), DCM (2.5 mL). 18 W blue light, air, rt, 5 h. Yields are based on Cyclohexane and detected by 1H NMR analysis using CH2Br2 as an internal standard.b DIB (0.155 mmol, 1 equiv), alkane (40 equiv), H2O (0.5 mL), DCM (2.5 mL) 18 W blue light, air, rt, 17 h. Yields were based on DIB and detected by 1H NMR analysis using CH2Br2 as an internal standard.
Many experiments were carried out in order to confirm the proposed pathway of activation of alkyl sp3 C−H bonds. As shown in scheme 2a, when TEMPO and BHT were added to the standard conditions of chlorination, bromination, and oxidation as radical scavengers, none of the corresponding products was detected, and compound 13 was detected by GC-MS, which indicated that the
transformations of chlorination, bromination, and oxidation proceed via a radical pathway.
In order to verify the source of oxygen involved in oxidation,18O-labelling experiments were carried out. When H216O was replaced with H218O as the nucleophilic reagent using adamantine as the substrate, 18O-labelled 1-adamantanol was obtained in 48% yields. The result shows that water acted as the oxygen source in the C−H oxidation of alkane.
Scheme 2 Study on the mechanism experiments
Finally, various concentrations of NaCl/KBr were utilized under the standard chlorination/bromination conditions with cyclohexane as substrate. An obvious linear relationship between the yield of chlorocyclohexane and the concentration of Cl- within the tested concentration range was observed, but the increase of concentration of Br- could not improve the yield of product and accelerate the reaction (see the Supporting Information) which showed a certain possibility for the ionic pathway in the second step of chlorination (path B).
Conclusions
In summary, we have developed a general, scalable method to activate sp3 C−H bonds of cyclic and linear alkanes with cheap DIB, and the method exhibits good compatibility with various coupling reagents. A variety of alkyl chlorides, bromides, alcohols, and ketones can be prepared in moderate to excellent yields from readily available alkanes without the use of any toxic, volatile and explosive reagents.
Experimental