The Significance of Halide in Grignard Reagents

Abstract

The optical activity of 1-phenylethanol from benzaldehyde and methyl chloride Grignard reagent coordinated with (+)2,3-dimethoxybutane is about one fourth of that found for the same product when bis-methyimagnesiun is the reagent. The difference has been attributed to the relative coordinating power of magnesium chloride versus the optically active ether.Grigilard reagents usually contain bound halogen because they are commonly prepared by corrosion of magnesium by means of an organic halide. Indeed, this process historically defines the reagent. However, these reagents may be rendered halogen free by the dioxane precipitation technique of the Schlenks (I) and the resultant solution of bis-organomagnesium also has been considered to be a Grignard reagent. We adhere to this extended definition largely because the amount of magnesium halide in a Grignard reagent is dependent on the type of halide and upon the method of reagent preparation. Thus a reagent series may exist with bis-organomagnesium a t one extreme and Grignard reagent saturated with magnesium halide a t the other. Such a series would be important only if there is a difference in reactivity in time or type between the extremes. Interest in these differences has increased during recent years (2, 3, 4). In this report the difference in coordination of the organometallic compound with an ether has been investigated.The method we used is the induction of optical activity in a product of Grignard reagent addition (5, 6, 7) by use of (+)2,3-diinethoxybutane to effect an asyinrnetric synthesis. We synthesized 1-phenylethanol from methyl Grignard reagent and benzaldehyde and compared yields and optical rotation when either bis-methylmagnesium or nlethyl chloride Grignard reagent is used. For the coinparison to be meaningful it is important that the first of these reagents be quite free from halide. Mosher (4) found it difficult to attain this condition. By contrast, our precipitate initially contains not only the halide in toto but also some of the halogenfree complex. T o obtain a reasonable yield of bis-methylmagnesium we must wash the precipitate thoroughly. Subsequently a small amount of white precipitate tends to appear in the solution, presumably because of temperature variations. I-Io~vever, both the solution and the slight precipitate are halogen free by silver halide test. The difference between our results and those of ibIosher may be due to our specific reagent or else to the dioxaneGrignard ratio or to our use of heat during the precipitation.The halide-free solution contains bis-methylmagnesium dioxanate or dioxanateetherate, so these ethers must be removed to ensure that the optically active ether will be fully effective. htlost of the diethyl ether is removed easily a t 50 "C under 1 atm of nitrogen, leaving a solid residue. Co~nparison of the weight of this residue with the basic magnesium equivalence, according to titration (S), indicates a composition of one-half dioxane per inole of bis-inethylmagnesium.

Catalytic Synthesis of Enantiopure Chiral Alcohols via Addition of Grignard Reagents to Carbonyl Compounds

“…18 Under these conditions, only the more reactive aldehyde and ketoester lead to the corresponding carbinols with slightly improved enantioselectivities respect to those reported by Wright. [14][15][16] Scheme 3. Addition of Grignard reagents to carbonyl compounds in the presence of (-)sparteine (L5) by Nozaki.…”