Critical reagents reactivity

Solvent Preparation. The most critical aspect of the solvent is that it must be dry (less than 0.02 wt % of H2O) and free of O2. If the H2O content is above 0.02 wt %, then the reaction of Mg and RX does not initiate, except for an extremely reactive RX species, such as benzyl bromide. Although adventitious O2 does not retard the initiation process, the O2 reacts with the Grignard reagent to form a RMg02X species. Furthermore, upon hydrolysis, the oxidized Grignard reagent forms a ROH species that may cause purification problems. 

The presence of Cu(i) or Cu(n) salts in the aforementioned reactions is critical. It is believed that organozinc reagents undergo transmetallation with copper species to yield more reactive complexes.301 A proposed301 catalytic cycle (Scheme 118) suggests that the alkyl group transferred to the enone from the copper metal in a bimetallic intermediate 207. 

The reaction conditions generally seem to be more critical with aluminum chloride than with stannic chloride. Yields, perhaps as a result, are more often hard to duplicate. These facts are doubtless due in part to the greater reactivity of aluminum chloride and to the difficulty commonly experienced in obtaining samples of this reagent which do not vary in catalytic effect. A pronounced influence of the grade of the aluminum chloride already has been mentioned. 

Metallated azoles frequently show expected properties, especially if not too many heteroatoms are present. Thus, Grignard reagents prepared from halogeno-azoles (see Section 3.4.3.9.3) show normal reactions, as in Scheme 154. 2-Lithioimidazoles react normally, e.g., with benzophenone (Scheme 155). Lithiated imidazoles are not always particularly reactive toward electrophiles and yields may be low. The nature of the quenching electrophile is the critical factor. Hard reagents like benzophenone tend to give better yields than the softer methyl iodide heteroaryl lithiums have hard carbanion centers. 

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