Epoxides , cleavage

Most recent publications by Hartshorn and his collaborators introduce a note of caution with regard to the mechanistic interpretation of results obtained in BF3-catalyzed epoxide cleavage reactions. They point out the marked dependence of the course of the reaction on the solvent used, either... 

Epoxides are cleaved by treatment with acid just as other ethers are, but under much milder conditions because of ring strain. As we saw in Section 7.8, dilute aqueous acid at room temperature is sufficient to cause the hydrolysis of epoxides to 1,2-diols, also called vicinal glycols. (The word vicinal means "adjacent/ and a glycol is a diol.) The epoxide cleavage takes place by SK2-like backside attack of a nucleophile on the protonated epoxide, giving a trans- 1,2-dio) as product. 

Identify the substitution pattern of the two epoxide carbon atoms—in this case, one carbon is secondary and one is primary. Then recall the guidelines for epoxide cleavages. An epoxide with only primary and secondary carbons usually undergoes cleavage by SN2-like attack of a nucleophile on the less hindered carbon, but an epoxide with a tertiary carbon atom usually undergoes cleavage by backside attack on the more hindered carbon. In this case, an S]sj2 cleavage of the primary C—O epoxide bond will occur. 

The A-D-ring analog 30a,b (mixture of epimers) has been prepared from the epoxide 3a,b by base catalyzed epoxide cleavage, hydroxymethylenation, and O-alkylation of the butenolide unit using standard conditions. Hydroxymethylenation of keto-ester 7 followed by butenolide addition provided the A-D-ring analog 31. 

The cleavage of epoxides by water is a classical reaction. Such epoxide cleavage can be catalyzed by both acids and bases in aqueous media. In the presence of other nucleophiles, the corresponding nucleophilic ringopening products are obtained with the nucleophiles being incorporated into the products.68 Examples include azides, iodides, and thiols in the presence or absence of metal salts in aqueous media. The pH of the reaction medium controls the reactivity and regioselectivity of the... 

Sn2 Reactions with epoxides and aziridines are also synthetically useful. An example of epoxide cleavage with an organocopper reagent with sp carbon moieties is the enantioselective synthesis of (3S, 4S)-4-methyl-3-heptanol (53), an elm bark beetle (Scolytus multistriatus) pheromone [42]. The chiral epoxy oxazolidine 51 [43], prepared from (R)-phenylglycinol, reacted with a propylmagnesium bromide-derived cuprate at —70 °C to afford the oxazolidine 52 in 74% yield (Scheme 9.12). Compound 52 was converted into the target molecular 53 by conventional procedures. 

Base-catalysed epoxide cleavage follows an 8 2 reaction in which the attack of the nucleophiles (NuA) takes place at the least substituted carhon of the ring. Therefore, hase-catalysed unsymmetrical epoxide produces 2-suhstituted alcohol. 

Hydroxy participation during the reductive epoxide cleavage cun also result in formation of new ether rings,. as indicated in th two examples shown in Eqa. (400) and (401). 

Stereoselective deoxygenation of epoxides. The ate complex [Bu3SnAl-(CH3)3] Li+ (1) formed from Bu3SnLi and A1(CH3)3 converts epoxides to alkenes with overall retention of stereochemistry. The results can be explained by inversion in the epoxide cleavage and antf-elimination of the Bu3Sn and O A1(CH3)3 groups. Example ... 

Step 2 Selective epoxidation of the more electron rich double bond. Step 3a Acid-catalyzed epoxide cleavage. 

Still other epoxide cleavage processes can be nucleophile induced, but without direct attack at a heterocyclic carbon. A good illustration of this phenomenon is seen in the alkylative elimination of epoxy tosylhydrazones (62). Optically pure allyl alcohols have been prepared... 

Prepared by addition of 4-pentenyl magnesium bromide to cyclopentanone, dehydration of the alcohol to l-(4-pentenyl)cyclopentene, epoxidation of the endocyclic double bond, and periodate epoxide cleavage.53... 

Alkylbis(t-butylphosphido)cuprates, RCuP(t-Bu)iLi.u These cuprates are obtained by reaction of RLi with [CuP(t-Bu)2]4. The cuprates are generally stable in THF at 25° for 4 hours, but can be used for conjugate addition, halide displacement (particularly of primary halides), and epoxide cleavage. 

The aspect of epoxide cleavage with the most potential is its ability to use the products of asymmetric epoxidation.64-65 Organolithium 45 is formed from 44 with Li and 5% DBB at -78 °C, and reacts with aldehydes and ketones to give enantiomerically enriched 1,2,4-triol derivatives such as 46. 

The reaction is an Sn2 epoxide cleavage with H as the nucleophile. The exact nature of the attacking nucleophile is not clear. 

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