Grignard reagent epoxide

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... 

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

Titanium alkyls, known as tamed Grignard reagents, do not add to esters, nitriles, epoxides, or nitroalkanes at low temperatures. Rather, they add exclusively ia a 1,2 fashion to unsaturated aldehydes (208—210). 

In terms of cost, the effectiveness of the catalytic cycle in the ring closure makes this process economical in palladium. The first three steps in the reaction sequence -- ring opening of an epoxide by a Grignard reagent, converison of an alcohol to an amine with inversion, and sulfonamide formation from the amine — are all standard synthetic processes. 

The introduction of alkyl groups into steroids is generally achieved by means of the following types of reactions between Grignard reagents and ketones or epoxides. 

The cleavage of steroidal epoxides with Grignard reagents leads exclusively to alcohols with the tra 5-diaxial orientation of the hydroxyl group and the newly introduced alkyl group. °... 

Simultaneous attack of the Grignard reagent on the epoxide and a,)5-unsaturated keto group in (6) provides the 6,16-dimethyl compound (7) after acetylation. 

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. ... 

An 11-ketone does not interfere, since it reacts only slowly with the Grignard reagent, and is unreactive in the subsequent epoxidation step. A series... 

The steroid epoxide rearrangement can occur with Grignard reagents only if both carbons of the epoxide ring are secondary. 

This kind of chemical reactivity of epoxides is rather general. Nucleophiles other than Grignard reagents react with epoxides, and epoxides more elaborate than ethylene oxide may be used. All these features of epoxide chemistry will be discussed in Sections 16.11-16.13. 

Nucleophiles other than Grignard reagents also open epoxide rings. These reactions are carried out in two different ways. The first (Section 16.12) involves anionic nucleophiles in neutral or basic solution. 

Grignard reagents do react with epoxides 24 by an SN2-mechanism, resulting in a ring-opening reaction. An epoxide carbon bearing no additional substituent—i.e. a methylene group—is more reactive towards nucleophilic attack than a substituted one ... 

Especially in the early steps of the synthesis of a complex molecule, there are plenty of examples in which epoxides are allowed to react with organometallic reagents. In particular, treatment of enantiomerically pure terminal epoxides with alkyl-, alkenyl-, or aryl-Grignard reagents in the presence of catalytic amounts of a copper salt, corresponding cuprates, or metal acetylides via alanate chemistry, provides a general route to optically active substituted alcohols useful as valuable building blocks in complex syntheses. 

The reaction between Grignard reagents or organolithium reagents and epoxides is very valuable and is often used to increase the length of a carbon chain by two... 

When gem-disubstituted epoxides (122) are treated with Grignard reagents (and sometimes other epoxides), the product may be 123, that is, the new alkyl group may appear on the same carbon as the OH. In such cases, the epoxide is isomerized to an aldehyde or a ketone before reacting with the Grignard reagent. Halohydrins are often side products. 

When the substrate is a vinylic epoxide, Grignard reagents generally give a... 

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