A detailed description of the mechanism of reaction of grignard reagents with ketones

Abstract

A detailed description of the reaction of Grignard reagents with ketones is presented based on several studies. The composition of Grignard reagents in Et20 and THF is described based on molecular association and NMR studies. The cause and mechanisms of formation of pinacol and hydrol in the reaction of “CH3MgBr” with benzophenone is also described. Several probes to detect the radical nature of the R group in RMgX and the radical anion nature of the ketyl produced in the reduction of the ketone, were used to study the electron transfer nature of Grignard reagent addition to ketones. The results of these- studies show clearly that Grignard reagents react with ketones by both a polar and electron transfer pathway. Which of these two pathways involves the lowest energy depends on the nature of the R group of the Grignard, the purity of the magnesium used to prepared the Grignard reagent. the nature of the ketone and the solvent. Grignard reagents that are difficult to oxidize (e.g. 1° R group), ketones that are difficult to reduce (e.g. lace-tone), solvents of low polarity (e.g., Et20) and Grignard reagents made from pure magnesium metal favor a polar pathway, and usually only 1,2-addition product is formed. On the other hand, Grignard reagents that are easily oxidized (e.g. 3° R group), ketones that are easily reduced, (e.g., Ph2C=0) solvents of high polarity (e.g., THF, HMPA) and Grignard reagents made from magnesium containing 1st row transition metals, favor an electron transfer pathway. Usually 1,2- and 1,6-addition products are formed as well as some pinacol. © IUPAC