Heterocyclic magnesium reagents

Examples of the preparation of other heterocyclic magnesium compounds are shown in Tab. 3.6. The preparation of Grignard reagents derived from bromofuran, bromothiophene, and bromoselenophene has been reported, but no synthetic application has been attempted [106]. 

A variety of functionalized heterocyclic Grignard reagents can be prepared using an iodine- or bromine-magnesium exchange reaction [45,79]. The electronic na-... 

Sensitive benzylic heterocyclic magnesium species such as 173 are readily obtained by a Br/Mg-exchange from the bromomethyloxazole 174. Grignard reagent 173 is generated at -78 °C in the presence of d-valerolactone in order to minimize self-condensation, leading to the hemi-ketal in 66% yield. This reaction was used by Smith in the course of the total synthesis of (-l )-phorboxazole A leading to intermediate 175 in 76% yield (Scheme 4.36) [100]. 

Oddo reported that the organomagnesium derivatives of p3Trole, indole, skatole, and carbazole could be prepared in a single operation by mixing the parent heterocyclic compound with an alkyl halide and magnesium in anhydrous ether.The product formed was reported to be the same as that obtained by the more conventional procedure. However, this approach to the synthesis of the indole Grignard reagents does not seem to have been exploited in subsequent work. 

This iodine-magnesium exchange can also be performed with heterocyclic iodides, such as the functionalized pyridine 16 [21] or the iodouracil derivative 17 (Scheme 2.5) [22]. In both cases, the intermediate organomagnesium reagent can... 

If we copy Nature rather more exactly, the Claisen ester condensation can be carried out under neutral conditions. This requires rather different reagents. The enol component is the magnesium salt of a malonate mono-thiol-ester, while the electrophilic component is an imidazolide—an amide derived from the heterocycle imidazole. Imidazole has a pK of about 7, Imidazolides are therefore very reactive amides, of about the same electrophilic reactivity as thiol esters. They are prepared from carboxylic acids with carbonyl diimidazole (CDI). 

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