Epoxide with Grignard

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. °... 

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... 

Reactions of Epoxides with Grignard and Organolithium Reagents... 

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

Reaction of acyclic propargyl epoxides with Grignard reagents in the presence of Cu catalyst afforded the S 2 products exclusively, with high stereoselectivity toward the syn-product. For the trans-epoxide, the selectivities are higher, particularly for the syn-process [32 Eq. (75) and Table 21]. 

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. 

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

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. 

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. 

In 1974, Vermeer et al. described formation of allenic alcohols 61 by the reaction of alkynyl epoxides 60 with Grignard reagents in the presence of 10mol% of Cul (Scheme 3.33) [71]. In the absence of Cul, a complicated mixture of products was obtained. Furthermore, the Cu-catalyzed reactions exhibited higher yields and higher selectivity than analogous reactions of alkynyl epoxides with lithium dialkylcup-rates [72], This method was applied to a reaction of allylmagnesium bromide with an alkynyl epoxide [73]. 

Reduction of acetals or ortho esters 0-80 Reduction of epoxides 0-92 Cleavage of acetals or ortho esters with Grignard reagents... 

Rearrangement of several substituted chlorohydrins of fixed conformation has recently been reported by Curtin and Harder,3M and attention is directed to this interesting paper, since it is related to the abnormal reaction of a-haloketonos with Grignard reagents and hence pertinent to epoxide chemistry,... 

In the seoond, the halogen is displaced nucleophilically by nxygen and a transient epoxide species is formed which, in the presence of MgXg, rearranges to a carbonyl compound. The latter in turn reacts with Grignard reagent to give the observed products. A similar mechanism has been advanced by House 13-814 in a related problem (Eq. 167. ... 

Although the iron-catalyzed synthesis of allenes from propargylic halides was reported by Pasto and coworkers in 1978 [67], little progress was achieved in this field until recently [68]. In 2003, Fiirstner and coworkers discovered propargylic epoxides as valuable substrates for the reaction with Grignard reagents in presence of catalytic amounts of Fe(acac)3 to generate 2,3-allenol derivatives (Scheme 5.24) [69]. 

Few types of epoxide react with Grignard or organolithium reagents in the absence of catalysts without rearrangement. These include oxirane, which has been extensively used to transform these organometallic reagents into 2-substituted... 

Scheme 4.67. Reaction of epoxides with organolithium and Grignard reagents[296, 310-313].

Write equations for the reaction of ethylene oxide or other epoxides with nucleophiles such as H+, and H20, H+ and alcohols, ora Grignard reagent. 

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