Magnesium—carbon bonds reactions with

Electrophilic functional groups in ortho-position to the carbon-magnesium bond allow two sequential alkylations. Starting from ort/io-iodobenzyl chloride 104, the benzannulated heterocycles 105 and 106 are obtained after the reaction with appropriate electrophiles (Scheme 8) . ... 

The reactivity of the 1,1 -diorganometallics (61) has been extensively investigated by Knochel and co-workers.9293 Since the reactivity of a carbon-lithium or a carbon-magnesium bond is considerably different from that of a carbon-zinc bond, a selective reaction of (61) with two different electrophiles is often possible. The general reaction pathways are summarized in Scheme 33. The addition of allylic zinc... 

Processes (b) and (c) are limited by diffusion and heat removal. The activation energies of these processes are low. Process (a) involves common chemical reactions and is improbable at low temperatures ( 80 K). Indeed, as already mentioned, only the most active organic halides with weakened carbon-halogen bonds react with magnesium immediately in the course of condensation. Therefore, only the aggregation and stabilization processes are actually important. Let us consider them in the light of quantum-chemical calculations. 

Other examples are summarized in Table 1. Terminal olefins nicely participated in this reaction as shown in Eq. (1) and entries 1 and 2 in Table 1. Styrene showed a reversal of regioselection relative to the position of the newly formed carbon-magnesium bond. However, sterically hindered olefins afforded an increasing amount of hydrogenated product, even after treatment of the reaction mixture with D2O (see Table 1, entries 3 and 4). Finally, no deuterated hydrocarbons were obtained from trans- and trisubstituted olefins, even though the starting materials were almost completely consumed (see Table 1, entries 5 and 6). 

Apart from differences in polarity of the carbon-magnesium bond, there may be other reasons why organomagnesium chlorides react faster than the other organomagnesium halides. This, then, may also cause a change in the composition of the reaction products, since slower reactions have no chance to develop, as in the reaction of neopentylmagnesium chloride with benzophenone in Scheme 4. 

The reaction of acetone with phenylmugnesium bromide is. however, very fast 2(>. In this reaction there ts ohviouslv no ileal lor ail initial breaking ol die carbon magnesium bond. Ill the reaction the new bonds are formal in concert with the breaking ol the old bonds. I he concerted reaction, however, rapines a close approach ol the two molecules. 

At higher temperatures, the elimination reaction is favored, and thus functionalized benzynes of type 314 are formed, which react with furan in [4-r2]-cycloaddi-tion (Scheme 4.69). Remarkably, benzyne 314 reacts with magnesium thiolates and amides as nucleophiles in an addition reaction, leading to a new carbon-magnesium bond, which can further react with a variety of electrophiles (Scheme 4.70) [170]. 

In some instances a carbon-carbon bond can be formed with C-nucleophiles. For example, 3-carboxamido-6-methylpyridazine is produced from 3-iodo-6-methylpyridazine by treatment with potassium cyanide in aqueous ethanol and l,3-dimethyl-6-oxo-l,6-dihydro-pyridazine-4-carboxylic acid from 4-chloro-l,3-dimethylpyridazin-6-(lH)-one by reaction with a mixture of cuprous chloride and potassium cyanide. Chloro-substituted pyridazines react with Grignard reagents. For example, 3,4,6-trichloropyridazine reacts with f-butyl-magnesium chloride to give 4-t-butyl-3,5,6-trichloro-l,4-dihydropyridazine (120) and 4,5-di-t-butyl-3,6-dichloro-l,4-dihydropyridazine (121) and both are converted into 4-t-butyl-3,6-dichloropyridazine (122 Scheme 38). 

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