Grignard reaction with epoxides

The reaction of Grignard reagents with epoxides is regioselective m the same sense Attack occurs at the less substituted carbon of the ring... 

In some cases products of rearrangement are obtained either partially or exclusively on treatment of Grignard reagents with epoxides. Thus, reaction of the 2/ ,3/ -epoxide (14) with methyl Grignard reagent affords a mixture of two epimeric secondary A-nor alcohols (15) in 80% yield and the tertiary hydroxy compound, 2a-methyl-5a-cholestan-2/f-ol (16) in 15 % yield. ... 

Linstrumelle, G. Lome, R. Dang, H. P. Cu-Catalysed reactions of allylic Grignard reagents with epoxides. Tetrahedron Lett. 1978, 4069-4072. 

The reactions of Grignard reagents with aldehydes and ketones give alcohols, reaction with acid chlorides and esters give tertiary alcohols, reaction with carbon dioxide to give carboxylic acids, reaction with nitriles give ketones, and reaction with epoxides give alcohols. 

Addition of 10% Cul to the reaction of allylic Grignard reagents with epoxides exerts a marked efiect on the regioselectivity. The catalyst also increases the rate of reaction. The a-products are also the main products when sufficient Cul is added to form the stoichiometric dialkyl cuprate of the Grignard reagent, but yields are lower than in the copper-catalyzed reaction. ... 

The reaction of Grignard reagents with epoxides, at first glance, appears to be an effective method for a two-carbon homoligation. However, there are several competing reactions that limit the use of this method. These deleterious reactions are formation of halohydrins, rearrangements, polymerization of the epoxide, and in asymmetric epoxides, regioselectivity issues. 

Reactions of substituted epoxides with Grignard reagents are often accompanied by rearrangement. Thus, organocuprates are better suited for carbon-carbon bond forming reactions with epoxides. For a detailed discussion of the preparation and reactions of organocuprates, see Section 7.5. 

Allylic halides couple effectively with vinyltin reagents to provide the corresponding 1,4-dienes in high yields.2 Like nickel- and palladium-catalyzed Grignard reactions with allylic ethers, this reaction also proceeds with net inversion of configuration at the allylic center. Similarly, vinyl epoxides react... 

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... 

Dideoxy-DL-hexoses were prepared from 137 in the following way the carbon atom chain of the substrate was extended to a seven-carbon atom chain by a low temperature Grignard reaction with methylmagnesium bromide. The product obtained, 145, was separately cis-hydroxylated (to stereoisomeric tetraols 14<) or epoxidized (to epoxides 147). Products 146 and 147 were hydrolyzed and subsequently subjected to Ruff degradation. Pairs of stereoisomeric 2,6-dideoxy-DL-hexoses could be separated by column chromatography. Essentially the same approach served for a synthesis of 2-deoxy-DL-eo f/ ra-pentose. In this case compound 138 (X = OH) was used as a substrate for epoxidation. 

B Reactions of Grignard Reagents with Epoxides (Oxiranes)... 

Once again, there are several possible syntheses of this compound. One possibility is an FGl to an alcohol. This alcohol can then be disconnected in two different places and prepared by a Grignard reaction with either an aldehyde or an epoxide. While the epoxide disconnection may have a slight advantage by breaking the TM into more nearly equal pieces, both routes involve readily available starting materials and represent acceptable syntheses. Another good... 

Bromoallylsilane has been prepared and exploited as an a- or y-hydroxypropenyl synthon in reaction of its Grignard derivative with epoxides followed by phenylselenodesilylation or phenylsulphenyldesilylation, respectively (Scheme 34) ° (c/. ref. 61). 

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