Grignard reagents synthesis from alkyl halides

The synthesis involves the nickel-catalyzed coupling of the mono-Grignard reagent derived from 3-alkyl-2,5-diiodothiophene (82,83). Also in that year, transition-metal halides, ie, FeQ3, MoCb, and RuCl3, were used for the chemical oxidative polymerization of 3-substituted thiophenes (84). Substantial decreases in conductivity were noted when branched side chains were present in the polymer structure (85). 

Sulfides, or thioethers, are sulfur analogues of ethers, and like ethers they can be either symmetrical (R2S) or unsymmetrical (RSR1, where R and R are different). Sulfides can be prepared from alkyl halides by a Williamson-type synthesis with sodium hydrogen sulfide, sodium thiolate or sodium sulfide from alkyl or aryl halides via the Grignard reagent (11) from alkenes by radical-catalysed addition of thiols or by reduction of sulfoxides (Scheme 9).2b... 

Methiodide derivatives of 2-alkyl-l-benzyl-2-imidazolines are central to a synthetic route to a-branched ketones (Scheme 3). The addition to the imi-dazolinium salt is sensitive to the nature of the nucleophile, only Grignard reagents prepared from primary alkyl halides giving useful yields. Attempts to reduce the salts, to afford a method for synthesis of aldehydes, virere not successful. 

This reaction can be used for the synthesis of hydrocarbons but it may also take place as a side-reaction during generation of a Grignard reagent from an alkyl halide and magnesium, then leading to formation of undesired side-products. 

The direct synthesis of Grignard reagents from enantiomerically pure alkyl halides has always resulted in a 1 1 ratio of the two possible epimers.83 Once formed, the two components of the reagent are configurationally stable. If the reactivity of the two epimers differs significantly, as in the case of MenMgCl (17) and NeomMgCl... 

The synthesis of 18 exemplifies the Grignard method. The reagent is made1 from the alkyl halide with magnesium metal in dry ether and combined, without isolation, with the electrophile— all steps being carried out under strictly anhydrous conditions. 

In a similar manner, Grignard reagents react with cyclic a,/3-dihalo ethers derived from 3,4-dihydro-l,2-pyran and tetrahydrofuran to form the corresponding 2-alkyl-3-halo derivatives. Thus, addition of 2,3 dibromotetrahydropyran to methylmagnesium halide at 0° followed by hydrolysis gives a 65% yield of 2-methyl-3-bromotetrahydropyran. These materials are valuable intermediates in the synthesis of olefinic alcohols (cf. method 99). 

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