Grignard reactions polar mechanisms

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. 

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. 

The SET mechanism is known to be operative for reactions of Grignard reagents and aromatic ketones such as benzophenone ". In reactions of Grignard reagents and aliphatic ketones and aldehydes, the polar mechanism seems to be major . The reactions of aliphatic ketones and aldehydes are more widely ntilized in organic syntheses. Thns, at first, the polar addition mechanism was examined. 

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. 

Developments after the early 1960s in the studies of mechanisms for reactions of Grignard reagents have made it possible to come to a clearer understanding of the general character of these mechanisms. A differentiation between a radical character of such reactions, on the one hand, and a concerted (polar) mechanism, on the extreme other hand, is becoming more and more evident. However, the details on the structure of intermediates and the sequence of the different reaction steps still require more studies. 

Magnesio-ene reaction, 46 47, 356 357 Mechanism of Barbier reaction, 406 407 Mechanism of Grignard reagents addition reactions. 219 248 concerted (polar), 221, 237 242 cyclic transition state see Mechanism of Grignard reagents, addition reactions, concerted [polar]) development of reactivity spectrum. 225-235, 246... 

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