Ethylene oxide reaction with Grignard reagents

We saw an example of nucleophilic ring opening of epoxides in Section 15 4 where the reaction of Grignard reagents with ethylene oxide was described as a synthetic route to primary alcohols... 

Hudrlik, P. F. Ahmed, M. E. Roberts, R. R. Hudrlik, A. M. Reactions of (triphenylsilyl) ethylene oxide with Grignard reagents (and with MgBr2). A reinvestigation./. Org. Chem. 1996, 61, 4395-4399. 

The reaction of Grignard reagents with ethylene oxide is valuable for lengthening the carbon chain by two carbon atoms in a one-step process. 

Reaction of ethylene oxide with Grignard reagents... 

A further complication in the reaction of Grignard reagents with epoxides is that isomeric products are often formed. Thus ethylene oxide reacts with n-butylmagnesium bromide to give a mixture of 1-hexanol and 2-hexanol 25... 

Reaction of Grignard reagent with ethylene oxide (16.10)... 

The Grignard reagent from 2-thenyl chloride can be obtained by the use of the "cyclic reactor.However, rearrangement occurs in its reaction with carbon dioxide, ethyl chlorocarbonate, acetyl chloride, formaldehyde, and ethylene oxide to 3-substituted 2-methylthio-phenes, Only in the case of carbon dioxide has the normal product also been isolated. 

Grignard reagents react with oxetane, a four-membered cyclic ether, to yield primary alcohols, but the reaction is much slower than the corresponding reaction with ethylene oxide. Suggest a reason for the difference in reactivity between oxetane and ethylene oxide. 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

In the example shown, reaction of a Grignard reagent with the epoxide electrophile ethylene oxide proceeds as expected, and after acidification results in formation of an alcohol that is two carbons longer than the original nucleophile. 

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