Alkylmagnesium hydrides

Detailed reviews on the structures of organomagnesium compounds and the constitution of their solutions have been published [D, 1, 2]. These references, especially the first two, also cover alkylmagnesium hydrides, amides, alkoxides and thiolates. However, while all of these compounds are of intrinsic interest, they are little used in synthesis. 

For application in synthesis, the most important of these are those where X = halogen and Y = alkyl the transformation of Grignard reagents into dialkylmagnesium compounds. Other transformations of this type are valuable for preparing alkylmagnesium hydrides (Y = H), alkoxides (Y = OR ), carboxylates (Y = OCOR ), amides (Y = NR 2, thiolates (Y = SR ), etc., but since most of these products are not extensively employed in synthesis these transformations are summarized only briefly. 

Aryl-alkenyl cross-coupling is straightforward. Simple alkylmagnesium reagents (Me, Et, CH2SiMe3, etc.) can be easily involved in Ni-catalyzed cross-coupling (27),139,140 while more complex alkyl halides—particularly branched ones prone to /3-hydride elimination—require Pd catalysts with bidentate phosphines, such as dppf, to achieve good selectivity (Section 9.6.3.4.7). 

Improved yields of cyclopropylamines 47 could be obtained by using methyltitanium triisopropoxide (53) instead of titanium tetraisopropoxide [108], as well as by adding the Grignard reagent to the mixture of the amide and the titanium reagent at ambient rather than low temperature (Schemes 11.15 and 11.16, and Table 11.9) [67,69]. In principle, methyltitanium triisopropoxide requires only one equivalent of the alkylmagnesium halide to generate a dialkyltitanium diisopropoxide intermediate 55, and in this particular case P-hydride elimination can only occur at the non-methyl substituent so that methane... 

Ethyl 3-ethoxy-a-nitroacrylate with 1,1-diphenylhydrazine in ethanol followed by heating has been shown to give l,4-bis(diphenylamino)-2,5-diethoxycarbonyl-l,4-dihydropyrazine (1586). A small amount of 2,5-dicyano-l,4-bis(dimethylamino)-1,4-dihydropyrazine was obtained from the reaction of 2-chloro-3-(2, 2-dimethyl-hydrazino)propionitrile [(Me)2NNHCH2CH(Cl)CN] with sodium hydride (1587). Hexaalkyl-l,4-dihydropyrazines and other 1,4-dialkyl-1,4-dihydropyrazines can be obtained by thermolysis of the products of reaction of a-(alkylamino)carboxylic acid esters with alkylmagnesium bromide. Thus the reaction of ethyl a-s-butyl-aminopropionate with ethylmapesium bromide, followed by heating in vacuo to 250-300°, gave 2,5-dimethyl-3,6-diethyl-l,4-di-s-butyl-l,4-dihydropyrazine (1588). 

Epstein, O. L., Savchenko, A. I., Kulinkovich, O. G. Titanium isopropoxide-catalyzed reaction of alkylmagnesium halides with ethyl acetate in the presence of styrene. Non-hydride mechanism of ligand exchange in the titanacyclopropanes. Tetrahedron Lett. 1999, 40, 5935-5938. 

The introduction of a polyfluorinated chain is not so easy as that of an alkyl chain. Transition metal catalyzed cross-coupling of Grignard reagents and organozinc compounds are inefficient in the synthesis of polyfluorinated 3-alkylthiophene. The copper-catalyzed perfluoroalkylation results in the formation of 2-and 3-substituted thiophenes, which are difficult to separate from each other. The reaction of fluorinated alkylmagnesium iodide with 3-formylthiophene, follwed by reduction with lithium aluminum hydride, gave (22) in an overall yield of 40% [27]. 

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