Sn2 Opening of Epoxides

FIGURE 6.8 Epoxides possess multiple electrophilic sites. 

FIGURE 6.9 For pyranose sugars, the Fiirst-Plattner rule predicts tran -diaxial relationships between nucleophiles and liberated hydroxyl groups. 

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Nucleophilic ring opening of epoxides has many of the features of an Sn2 reaction. Inversion of configuration is observed at the carbon at which substitution occurs. 

Polymerization using epoxides as monomers includes the ring opening of epoxides via C-O bond cleavage. Thus, a mode of G-O bond cleavage (Sn2 or SnI) and selectivity, that is, which C-O bond is cleaved, coupled with the symmetry of epoxides (symmetrical or unsymmetrical), cause regio- and stereochemical issues to be controlled in the epoxide polymerization. 

Following these general examples, we can now analyze the opening of epoxides in more detail. The size of the ring imposes geometric constraint and the SN2 reaction demands colinearity. The approach of the nucleophile should then resemble J7. + which is different from that in displacement of a leaving group on an aliphatic chain, i. e. 19 20. 

Fig. 3.42. Mechanism and energy profile of trans-selective additions to C=C double bonds. The first step, the formation of the onium ion, is rate-determining. The second step corresponds to the Sn2 opening of an epoxide.

Hydride Reduction of a Carbonyl Group 454 Reaction of a Tertiary Alcohol with HBr(S[ 1) 480 Reaction of a Primary Alcohol with HBr (SN2) 480 Reaction of Alcohols with PBr3 485 (Review) Acid-Catalyzed Dehydration of an Alcohol 487 The Pinacol Rearrangement 495 Cleavage of an Ether by HBr or HI 639 Acid-Catalyzed Opening of Epoxides in Water 649 Acid-Catalyzed Opening of an Epoxide in an Alcohol Solution 650... 

Under anionic conditions, the ring opening follows an Sn2 mechanism. Thus, the ring opening of The nng opening of epoxides. , ., o r o. , , ... 

Nucleophilic ring opening of epoxides with heteroatom nucleophiles is another valuable method for the synthesis of many heteroatom-modified carbohydrate derivatives. The cyclic nature of epoxides renders the competing elimination process stereoelectronically unfavorable. Analogous to the above-discussed Sn2 nucleophilic mechanism, nucleophiles can open epoxide rings, and give rise to Walden inversion at the attacked carbon, furnishing a-hydroxy derivatives as illustrated in O Scheme 10. 

Nucleophilic substitutions proceeding via Sn2 pathways can be activated by pressure, as has been demonstrated in many examples. In particular, the ring opening of epoxides can be initiated by pressure, and also by Lewis acid catalysis. Consequently, combining these two activation modes might lead to an even more effective way to functionalize epoxides, and indeed, this strategy has been successfully applied. 

Epoxides are typically synthesized through peracid-mediated additions to aikenes. Opening of epoxides in either acid or base is stereospecifically trans (here is the Sn2 reaction at work), but the regiochemistry of opening depends on the conditions. In base, steric factors lead to addition of the nucleophile at the less hindered position. In add, the nucleophile adds predominantly to the protonated epoxide at the more sterically hindered carbon. 

Substitutions of Sn2 type are frequently used for carbon-carbon or carbon-heteroatom bond formation. However, little attention has been devoted to the development of such reactions in water. This is likely due to concerns about competitive hydrolysis of the electrophile in water and SN2-type reactions being slower in aqueous conditions than in aprotic polar solvents due to the higher cost of desolvation of nucleophiles. We shall discuss the ring opening of epoxides and aziridines, palladium-catalyzed allylic substitutions, as well as acylations and sulfonylations of amines and alcohols. 

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