Polar mechanisms, Grignard carbonyl

The addition of RLi and other nucleophiles to carbonyl functions in general proceeds via one of the two possible reaction pathways, polar addition (PL) and electron transfer (ET)-radical coupling (RC) sequence (equation 5). Current reaction design for the synthetic purpose of additions of common nucleophiles to aldehydes and ketones is mostly based on the polar mechanism, but apparently the ET process is involved in some reactions of, for example, Grignard reagents Mechanistically there are three possible variations the PL pathway, the ET rate-determining ET-RC route and the RC rate-determining ET-RC route. 

If the addition of a Grignard reagent to a carbonyl compound leads to the formation of such an unexpected alcohol, it is clear that this reaction cannot have proceeded according to the polar mechanism outlined in the upper row of Figure 10.27. If the respective addition does not produce anything hut the expected alcohol, the polar mechanism provides the easiest explanation. Nevertheless, the radical mechanism could also have applied—provided, though, that the isomerization H —> iso-H would have been much slower than the radical annihilation reaction H — I. 

In spite of various theoretical studies of Grignard reactions shown in the previous section, their mechanisms seem to be as yet unsettled. In particular, the connection between the R MgX dimer in the Schlenk equilibrium and its reactivity toward carbonyl groups is still unclear. In this section, a systematic computational study of several Grignard reactions is presented in order to reveal their unclear points. The polar vs. SET problem will be explained in a forthcoming new mechanism. 

In 1929 Blicke and Powers (."il suggested that some carbonyl compounds may react with Grignard reagents by stepwise, homolytic reaelioti mechanisitis, but more than 40 years passed before this theory was generally accepted. The homolytic mechanism and the polar concerted ntoehanism are show ll in. Scheme l.l. 

For the mechanism of the metal-mediated Grignard-type reactions in water, Li previously proposed a carbanion/allylmetal/radical triad, in which the specific mechanism of the reaction is dependent on the metal being used (Fig. 4.6). Recently, mechanistic studies of the aUylation detected secondary deuterium kinetic isotope effects in the metal-mediated aUylation ofbenzaldehyde in aqueous media.The inverse SDKIE observed for the indium and tin cases are consistent with the polar addition mechanism. For magnesium and antimony, normal SDKIE were observed. These were interpreted as single electron transfer processes on metal surface in the magnesium case, or between the allyhnetal and the carbonyl compound in the antimony case. 

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