Grignard reagent choice

There is often a choice of two or more different substrates which can give rise to the same product with different Grignard reagents. Thus l,l-diphen5i-ethanol [599-67-7] can be prepared by three different routes, as shown in Figure 2. The choice depends on the yield and ease of purification as well as the cost of the substrate and the Grignard reagent. 

IV-substituted and B-substituted borazines are readily prepared by suitable choice of amine and borane starting materials or by subsequent reaction of other borazines with Grignard reagents, etc. Thermolysis of monocyclic borazines leads to polymeric materials and to polyborazine analogues of naphthalene, biphenyl, etc. ... 

Chelation control does not operate in the addition of 2-butenyl Grignard reagents to a-oxyalkanals, since with (racemic) 2-benzyloxy-, 2-(benzyloxymethoxy)- and 2-(t< rt-butyldi-methylsilyoxy)propanal similar ratios of isomers are formed28. Several cations were investigated, but the best choices, e.g., allylboronates or allylsilanes, were not included in this study. 

The enantioselective addition of organometallic reagents to, V-(trimethylsilyl)benzaldehyde imine (1) in the presence of enantiomerically pure modifiers has been investigated. The best result is obtained with butyllithium (the corresponding Grignard reagent affords both lower yield and selectivity, 1 fails to react with diethylzinc) and two equivalents of the enantiomerically pure diol 2 in diethyl ether. It should be noted that the choice of the solvent is crucial for the stereoselectivity of the reaction1 2 3 5 7 8 9. 

More typical examples are the amino ethers (3) used as anti-histamine or anti-Parkinson drugs according to the substituents. These are obviously derived from the alcohols (4) which are made from an aryl Grignard reagent and a benzaldehyde. Either starting material may bear the substituent X the choice can be made according to availability and so that side reactions are avoided,... 

THF is used as solvent for this reaction (Scheme 156). Indeed, THF is the solvent of choice for the alkylation of N- oxides by Grignard reagents. The following references (B-71MI20500, 74HC(14-S2)i) should be consulted for a more comprehensive coverage of these reactions. Reactions of the above type with organolithium compounds are less successful as metallation becomes a major pathway (vide infra). 

In the cyclic series several examples, as summarized above, have been provided. The diastereoselectivity, l or u, essentially can be controlled by the choice of the halide in the Grignard reagent and the additive, i.e., employing either organomagnesium bromide with copper(I) bromide and a phosphine, or organomagnesium chloride with copper(I) bromide and chlorotrimethylsilane (see also syn/anti selectivity in Section 1.1.1.2.). 

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