Epoxide opening Grignard reagent

Rearrangement of epoxides with magnesium salts means that opening epoxides with Grignard reagents can give surprising results. 

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... 

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. 

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 ... 

When dienones such as 55 are subjected to the epoxidation conditions the electron-poorer C=C double bond is selectively epoxidized. The other C=C bond can be functionalized further, for example, it can be dihydroxylated, as shown in the synthesis of the lactone 56 (Scheme 10.11) [82]. Stannyl epoxides such as 57 (Scheme 10.11, see also Table 10.8, R1 = n-Bu3Sn) can be coupled with several electrophiles [72], reduction of chalcone epoxide 58 and ring opening with alkyl aluminum compounds provides access to, e.g., the diol 59 and to phenylpropionic acids (for example 60). Tertiary epoxy alcohols such as 61 can be obtained with excellent diastereoselectivity by addition of Grignard reagents to epoxy ketones [88, 89]. 

Mechanism 14-4 Base-Catalyzed Opening of Epoxides 653 14-14 Orientation of Epoxide Ring Opening 654 14-15 Reactions of Epoxides with Grignard and Organolithium Reagents 656 14-16 Epoxy Resins The Advent of Modern Glues 656 Summary Reactions of Epoxides 658 EssentialTerms 660 Study Problems 662... 

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