Halogeno-Metal Electrophiles

In 1992, Julia et al. [147] employed halomethylmagnesium halides [148] instead of halomethyl starmanes. This process allows the replacement of the sulfonyl group of primary and secondary alkyl sulfones by methylene and alkylidene chains with great success (Table 3.14). 

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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. 

Schemes 9-3 and 9-4 are sequences of two substitutions, first a metallo-de-hydrogenation, followed by a halogeno-de-metallation. Scheme 9-3 is analogous to the well known electrophilic aromatic sulfonation of anthraquinone in position 1. This isomer is obtained only if the reaction is run in the presence of catalytic amounts of mercury (ii) salts. Nowadays, however, larger effort is devoted to either replace mercury by other catalysts, or in the search for processes leading to (practically) complete recovery of the mercury. This case raises two questions with respect to the reaction sequence (9-3) first, whether it is possible to apply a one-pot process with catalytic amounts of a mercury compound (not necessarily HgO) to the synthesis of compounds 9.5, and second, whether mercury can be completely recycled in processes using either stoichiometric or catalytic amounts of the element.

A few years back, electrophilic-induced cychzations to access oxygen-containing heterocycles required a stoichiometric quantity of an electrophile such as iodine, phenylselenium hahdes, or N-halogeno succinimides. Over the past decades, metal-catalyzed cychzations induced by a variety of metal salts centered on Pd, Au, Pt, Co, Mn, Ru, Hg, Os, Fe have emerged. It is worth mentioning that some metals are more specifically used to produce THFs (e.g., Ru, Os, Mn), others to afford THPs (e.g.. Fig, Pd, Pt, Au), and others to synthesize spiroketals (e.g., Pd, Ir, Pt, Au). The choice of the metal is related to the structure of the precursor which can be transformed to the desired oxygen-containing heterocycle. 

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