Nucleophilic Ring-Opening of an Epoxide

Nucleophilic Ring-Opening of an Epoxide THE OVERALL REACTION  

Step 1 The nucleophile attacks the less crowded carbon from the side opposite the carbon-oxygen bond. Bond formation with the nucleophile accompanies carbon-oxygen bond breaking, and a substantial portion of the strain in the three-membered ring is relieved as it begins to open at the transition state. 

Step 2 The alkoxide rapidly abstracts a proton from the solvent to give the (3-azido alcohol as the isolated product. 

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However, these have not been the only approaches to the synthesis of these ring systems. For example, Sasaki et al. were able to use an intramolecular nucleophilic ring opening of an epoxide with sodium dimsylate to form the oxepane ring as illustrated in the conversion of 34 to 35 <99JOC9399>. 

Enolates can react with many electrophilic species other than alkyl halides, analogous to the reactions of other carbanions (Chap. 8). Nucleophilic ring opening of an epoxide to give alcohols is very common, occurring at the less sterically hindered carbon. l Grieco et al. used the dilithio salt of acetic acid (LiCH2C02Li,... 

The key to the success of the vinyl epoxide route would reside in a nucleophilic ring-opening of vinyl epoxide 75. If this ring-opening proceeds regioselectively at C5 via a SN2 pathway, it would have been the most welcome at this stage of our efforts (Scheme 8.21). However, an array of conditions, including Pd(0)-mediated and Lewis acidic conditions, were screened over a period of almost 2 years, but we never observed the desired 1,4-diol 80. Instead, we could at various times see small... 

Metal oxides were also chirally modified and few of them showed a significant or at least useful e.s. Thus, while Al203/alkaloid [80] showed no enantiodifferentiation, Zn, Cu, and Cd tartrate salts were quite selective for a carbene addition (45% e.e.) [81] and for the nucleophilic ring opening of epoxides (up to 85% e.e.) [82], Recently, it was claimed that /(-zeolite, partially enriched in the chiral polymorph A, catalyzed the ring opening of an epoxide with low but significant e.s. (5% e.e.) [83], All these catalysts are notyet practically important but rather demonstrate that amorphous metal oxides can be modified successfully. 

One synthesis of benzofurans is based on cyclofragmentation. An appropriately substituted sulfone is used as a nucleophile in intramolecular ring opening of an epoxide. The resulting molecule loses a sulfinate and formaldehyde. By immobilization of the sulfinate on a resin this sequence can be used for the cleavage of benzofurans from solid supports [112] (Scheme 6.1.31). 

The nucleophilic ring opening of meso-epoxides leads to chiral products. Control over the position of attack will provide an enantiomerically enriched product, as shown in Figure 12.2, where cyclohexene oxide (12.116) undergoes ring-opening to produce either compound (12.117) or its enantiomer (e t-12.117). °... 

In a base-catalyzed ring opening of an epoxide, the nucleophilic attack is on the less substituted (less hindered) carbon atom in the epoxide ring. The mechanism is shown below. 

Chiral epoxides can be transformed into many useful chiral building blocks via reductive cleavage or nucleophilic ring opening of an oxirane ring. Yang and Zhou... 

Nucleophilic ring-opening of meso-epoxides has long been recognized as an approach to provide access to useful building blocks for asymmetric... 

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... 

Nucleophilic ring opening of epoxides has many of the features of an 8 2 reac tion Inversion of configuration is observed at the carbon at which substitution occurs... 

As we ve just seen nucleophilic ring opening of ethylene oxide yields 2 substituted derivatives of ethanol Those reactions involved nucleophilic attack on the carbon of the ring under neutral or basic conditions Other nucleophilic ring openings of epoxides like wise give 2 substituted derivatives of ethanol but either involve an acid as a reactant or occur under conditions of acid catalysis... 

Nucleophilic ring opening of epoxides by ammonia (Section 16 12) The strained ring of an epoxide is opened on nucleo philic attack by ammonia and amines to give 3 ammo alcohols Azide ion also re acts with epoxides the products are p azido alcohols... 

Using the catalytic system described above, the enantioselective opening of meso epoxides could also be pursued. Although many excellent examples of ring-opening of meso epoxides by Sn2 reactions have recently been reported, the reaction planned here is conceptually different [40]. In the SN2 reaction, the path of the incoming nucleophile has to be controlled. In the titanocene-catalyzed reaction, the intermediate radical has to be formed selectively. If an intermediate similar to that invoked in the Bartmann ring-open-... 

A model system consisting of methyloxirane, formate, and formic acid has been used to study the nucleophile-catalysed and nucleophile- and acid-catalysed opening of an epoxide ring by applying ab initio quantum mechanical calculations [up to the MP4(SDQ)/6-31- -G //MP2/6-31- -G" level] and also density functional theory... 

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