The ability to form C=C bonds at the target position has always been of high interest to synthetic chemists. Recently, Guo et al. reported a method by which to activate a hydrogen at the alpha position of a ketone to form a new C = C bond at that position (Figure 1).1 His method requires no metal catalysts, uses readily available starting materials, and requires no foreign reagents. DMSO is important in this reaction because it serves as a methylene source.
Figure 1: DMSO as a Carbon Source in the α-Methylation of Ketones.
Figure 1 shows the optimized conditions for the reaction. The performance of the reaction with various substances attached to the aromatic ring (electron-donating to electron-withdrawing) at positions 2, 3, and 4 gave yields that were generally good. (The 4-bromo substrate gave a yield of 42% which was the only example with a yield below 50%.)
These researchers R. also changed the nature of1, and they found that the response was also tolerant to changes in this condition. For example, R. change1 A methyl to a propyl group changed the yield from 72% to 67%, respectively.
This work also explored the mechanism of the reaction. They showed that the addition of the radical inhibitors did not significantly change the outcome of the reaction. This indicated that the reaction does not proceed through a radical pathway. They also reacted with the oxidized alpha carbon (α-aldehyde and α-carboxylic acid) starting with ketones. These reactions yielded none of the methylated product. This implies that the ketone does not undergo oxidation at the alpha position during the reaction. when they started the reaction with thiomethyl compound C, it proceeded smoothly for the product. This was a strong indication that the compound C formed during the reaction. Additionally, they ran the reaction with inactive DMSO resulting in =Cd2 in alpha position.
With these findings, the mechanism seen in Figure 2 was proposed. The ketone containing alpha hydrogen undergoes precipitation to form the enolate ion (a) Simultaneously, DMSO reacts with potassium persulfate to form anion b, ion b The compound undergoes nucleophilic attack by A to form C, forward reaction of the compound C Potassium persulfate results in the loss of methanethiol and the formation of a carbon-carbon double bond.
Figure 2: Proposed Mechanism.
Finally, these researchers have developed a metal-free method to form a new C=C bond at the alpha position of a ketone. The method has wide substrate scope and uses readily available reagents. DMSO plays an important role in the reaction, as it provides the electrophilic methylene group that undergoes nucleophilic attack by the enolate carbon. This reactive methylene source is readily provided by the reaction of DMSO with potassium persulfate.