Configuration inversion with Grignard reagents

Reactions of organomagnesium compounds with dialkyl sulfates or alkyl sulfonates often give satisfactory yields of the products of displacement of sulfate or sulfonate. Side-reactions have been observed, but they can often be avoided for example, an excess of the sulfate or sulfonate should be used with Grignard reagents, as some is consumed by nucleophilic attack by halide ion [A]. The dialkyl sulfates are reactive, but hazardous. Toluenesulfonates (tosylates) are less reactive, but their reactions are catalysed by copper complexes the reactions of trifluoromethanesulfonates (triflates) are catalysed by nickel complexes. Reactions of Grignard reagents with secondary tosylates appear to follow an Sn2 mechanism, with inversion of configuration [43],... 

In all cases, the major diastereoisomer (9) is crystalline. The sulfinate esters (9a-d) undergo clean reaction with Grignard reagents to yield sulfoxides in good yield and with complete inversion of configuration at sulfur as highhghted in Scheme 2.12. 

Marino has reported that cyclic a, -unsaturated epoxides react with Cu carboxylates, generated in situ from Na carboxylates and CuCl, to give xy -l,4-diol derivatives.Goering has shown that allyl pivalates give a-alkylation with inversion of configuration with Grignard reagents catalyzed by CuCl, but (anti) y-alkylation with copper(I) cyanide as catalyst. ... 

Homoallylalcohols are obtained by an iron-catalyzed regioselective and stereoselective substitution of Y,5-epoxy-a,P-unsaturated esters and amides with Grignard reagents (Scheme 4-201). The reaction proceeds with inversion of the configuration at the attacked C4 carbon atom and involving an Ti -allyliron intermediate. ... 

When a sulfonate ester possessing this type of chirality was converted to a sulfone with a Grignard reagent (10-129), inversion of configuration was found. This is not incompatible with an intermediate such as 147 but it is also in good accord with an Sn2 like mechanism with backside attack. 

C. Reactions of Phosphoric and Phosphinic Acid Derivatives.—The optically active phosphinate ester (90) has been shown to react with benzyl Grignard reagents or lithium anilide with inversion of configuration. Oxidation of... 

A further selectivity is found with the preferential displacement of aromatic ester linkages compared to alkyl ester linkages using Grignard reagents.41 In the reaction of the chiral mixed-ester phosphonite shown in Equation 4.17, preferential displacement of the aromatic ester compared to the alkyl ester occurs with inversion of configuration at phosphorus.42... 

Reaction of Grignard reagents with optically active sulfinate esters (150) is a particularly useful route to optically active sulfoxides and occurs with 100% inversion of configuration (Andersen et al., 1964). Substitution reactions of... 

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