Grignard reagents and esters

Grignard reagent and esters, 6, 32 Grignard reagent and ethylene oxide, , 54... 

Symmetrical alcohols can in fact be made in one step from Grignard reagents and esters, as the reaction first produces the aldehyde 57 which is more electrophilic than the ester and so reacts again. There is a warning here Aldehydes cannot be made by acylation of Grignard reagents with esters. But if two reactions are wanted, this is a good method. 

This reaction was first reported by Behai and Sommelet in 1904. It is the transformation of methyl -hydroxylalkyl ethers into aldehydes in the presence of acids, preferably oxalic acid. The methyl j -hydroxylalkyl ethers can be prepared via the Grignard Reaction between the Grignard reagents and esters of a-methoxy acetic acids. 

The mechanism is similar to the reaction between a Grignard reagent and ester, as illustrated here. 

Fatty acid esters have been synthesized in good yield by reaction between cuprate complexes, formed from methylcopper(I) and primary or secondary Grignard reagents, and esters of primary iodoalkylcarboxylic acids. This procedure provides the most direct route presently available to a variety of representative classes of simple fatty acids (Bergbreiter and Whitesides, 1975). 

Anilides or p-toluidides of acids from esters. Esters are converted into the corresponding anilides or p-toluidides by treatment with anilino- or with p-toluidino-magnesium bromide, which are readily obtained from any simple Grignard reagent and aniline or p-toluidine ... 

Among the methods for preparing carboxylic acids carboxylation of a Grignard reagent and preparation and hydrolysis of a nitrile convert RBr to RCO2H The malonic ester synthesis converts RBr to RCH2CO2H... 

The reaction involves nucleophilic substitution of for OR and addition of R MgX to the carbonyl group. With 1,4-dimagnesium compounds, esters are converted to cyclopentanols (40). Lactones react with Grignard reagents and give diols as products. 

Section 20.9 Esters react with Grignard reagents and are reduced by lithium aluminum hydride (Table 20.4). 

The conversion of a nitrile R —CN into a ketone R —CO—R demonstrates that polarized multiple bonds other than C=0 also react with Grignard reagents, and that such reactions are synthetically useful. Esters 22 and acid chlorides can react subsequently with two equivalents of RMgX the initially formed tetravalent product from the first addition reaction can decompose to a ketone that is still reactive, and reacts with a second RMgX. The final product 23 then contains two substituents R, coming from the Grignard reagent ... 

Reaction between Grignard reagents and ortho esters... 

The formation of halogenation products from Grignard reagents and sulfonic acid anhydrides is the result of an oxidative reaction pathway . This side-reaction can be reduced by using sulfonic acid esters, however, in these cases alkylations as well as twofold sulfonylations (cf. corresponding results with sulfonyl fluorides ) are competing (equations 64 and 65). 

The initial addition product is unstable and loses a magnesium alkoxide to form a ketone which is more reactive toward Grignard reagents than esters. 

Table 11.5. Substituted cyclopropanols 31 from carboxylic acid esters and alkenes via ligand-exchanged titanium intermediates generated from Grignard reagents and XTi(OiPr)3 (X = OiPr, Cl, Me).

Grignard reaction and similar transformations allow C-C bond formation without a palladium catalyst. Grignard reagents and organolithium compounds are very versatile carbanion sources used in the synthesis of acyclic, heterocychc and carbo-cychc compounds. The esters, ketones and aldehydes are more stable when the reaction takes place on solid supports than in the hquid-phase, because this immo-bihzed components are not so sensitive towards water or oxygen. In the total synthesis of (S)-zearalenone (155) on solid supports the Grignard reaction is one of the key steps (Scheme 3.16) [120]. 

The reactions here described are of considerable general utility for the preparation of a variety of fatty acids from the addition products of Grignard reagents and ./3-unsaturated esters.4-9... 

Transetherification 0-79 Reduction of ortho esters 0-92 Reaction between Grignard reagents and ortho esters... 

The procedure described4 is a modification of the method of Khotinsky and Melamed,8 who first reported the preparation of boronic acids from Grignard reagents and borate esters. Benzeneboronic acid and the corresponding anhydride also have been prepared by reaction of phenylmugnesium bromide with boron... 

---