PREPARATION OF HIGHLY REACTIVE MAGNESIUM AND ITS APPLICATION TO ORGANIC SYNTHESES (GRIGNARD, TOSYLATES, NITRILES)

A history of the activation methods used in Grignard reagent preparation is presented, along with recent activation studies for the preparation of highly reactive magnesium via alkali metal reduction. The method of choice involves reduction of MgCl(,2) by lithium in tetrahydrofuran, using a catalytic amount of naphthalene as an electron carrier; room temperature is preferred for reduction. Once generated, the magnesium powder may be used in reactions at reduced or elevated temperatures. The preparation of some difficult Grignard reagents has been accomplished; thus the Grignard reagent from 3-bromo-1-phenoxypropane has been successfully formed and cross-coupled with CO(,2) and benzoyl chloride to give the corresponding acid and ketone, respectively, in moderate yield. Another ethereal halide, 2,2-dimethyl-4-chloromethyl-1,3-dioxolane was found to be inert toward the activated magnesium. New frontiers were also explored. The activated magnesium was not found suitable for Simmons-Smith chemistry. However, it was found to exhibit remarkable reactivity towards several functional groups; ethers, tosylates, and nitriles acted as pseudo-halogens to form Grignard reagents under relatively mild conditions. The nitriles and tosylates showed a tendency to polymerize. The direct action of magnesium on aryl and alkyl nitriles to form triazines and imidazoles, in the former case, and pyrimidineamines, in the latter case, were previously unknown. Attempt to form Grignard reagents containing remote nitriles, esters or ketones, were generally unsuccessful, except in the case of 8-bromooctanenitrile, which is believed to be the first example of a Grignard reagent containing the nitrile functionality. Aromatic nitriles were reduced. The heteroatoms of the alkyl systems were strongly coordinated to the surface of the metal at the low temperatures required to prevent secondary attacks of the Grignard reagents on the functionality present, thereby preventing formation of Grignard reagents