Epoxide opening acid catalysed

The 9 — 15 fragment was prepared by a similar route. Once again Sharpless kinetic resolution method was applied, but in the opposite sense, i.e., at 29% conversion a mixture of the racemic olefin educt with the virtually pure epoxide stereoisomer was obtained. On acid-catalysed epoxide opening and lactonization the stereocentre C-12 was inverted, and the pure dihydroxy lactone was isolated. This was methylated, protected as the acetonide, reduced to the lactol, protected by Wittig olefination and silylation, and finally ozonolysed to give the desired aldehyde. 

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... 

A simple example of a ring-opening substitution reaction is the acid-catalysed hydrolysis of epoxides. In the example shown, protonation of the epoxide oxygen improves the leaving group, and an Sn2 reaction may then proceed using water as the nucleophile. Three-membered rings must of necessity... 

Squalene is an important biological precursor of many triterpenoids, one of which is cholesterol. The first step in the conversion of squalene to lanosterol is epoxidation of the 2,3-douhle bond of squalene. Acid-catalysed ring opening of the epoxide initiates a series of cyclizations, resulting in the formation of protesterol cation. Elimination of a C-9 proton leads to the 1,2-hydride and 1,2-methyl shifts, resulting in the formation of lanosterol, which in turn converted to cholesterol by enzymes in a series of 19 steps. 

Stereo- and regio-selective epoxidation of tricyclic trienes, such as (36), followed by Lewis acid-catalysed opening of the resulting monoepoxide with alcohols, has been reported to occur exclusively at the vinyl terminus of unsaturated system through a typical S 2 process, affording 1,6-dioxygenated derivatives (e.g. 37).49... 

We ll start with the acid-catalysed reaction, because it is more similar to the examples we have just been discussing—opening happens at the more substituted end. Protonation by acid produces a positively charged intermediate that bears some resemblance to the corresponding bromonium ion. The two alkyl groups make possible a build-up of charge on the carbon at the tertiary end of the proto-nated epoxide, and methanol attacks here, just as it does in the bromonium ion. 

What about the regioselectivity The obvious explanation is that a cation is formed from die epoxide in a specific acid-catalysed ring opening. But why should the nitrile attack the bottom face of the cation We should expect it to attack the top face preferentially as die hydroxyl group partly blocks the bottom face. 

The deracemization of rac-1-methyl-1,2-epoxycyclohexane (64) (Fig. 18.23) has been demonstrated by cells of Corynebacterium sp C12 and Methylobac-terium sp. (Archer et al., 1996 Ueberbacher et al., 2005). A one pot combination of Corynebacterium C12 epoxide hydrolase and acid catalysed ring opening converted rac-1-methyl-1,2-epoxycyclohexane to (1-S, 2-5)-1-methyl-cyclohexane-1,2-diol. Alternatively, instead of the chemical conversion of the unreacted oxirane, the formed diol can be converted into the remaining epoxide (Monfort et al., 2004). 

The alkene substrate is first dispersed in the reactor with the carboxylic acid in the presence of a solvent if necessary. Addition of hydrogen peroxide forms the peracid which facilitates epoxidation, and re-generates the carboxylic acid for further reaction. In consequence only low levels of carboxylic acid are required (0.2-0.3 mol per mol of double bond). This also has the advantage of reducing epoxide loss to acid-catalysed ring-opening. The application of two phases with or without the presence of solvent also improves the efficiency of the epoxidation. Peracids most suited to epoxidation in situ are performic and peracetic acid. 

Bearing in mind the stereochemistry of epoxide 11, propose a mechanism for its acid-catalysed ring opening under the conditions of step o. 

Participation by neighbouring ester groups was observed in acid-catalysed opening of 3jS"acyloxy-4a,5a-epoxides 4) [39]> which are conformationally ideal for giving a 3, 4 -acylonium bridge (5) (c/ p. 58). The intermediacy of structure (5) results in migration of the acyloxy group from C(3) to C(4) (6), and has been confirmed by the isolation of a stable... 

The chemistry of epoxides is dominated by the basicity of the oxygen lone pairs and the release of ring strain as the three-membered ring opens. Many of the reactions of epoxides are acid or Lewis acid catalysed. The catalyst may coordinate with the oxygen, increasing the polarity of the C -O bond and the sensitivity of the carbon atom to reaction with a nucleophile. The reactivity of epoxides are summarized in Box 2.5. 

Ring-opening of Epoxides. A full report has now appeared of the acid-catalysed hydrolysis of 5,6-epoxides in largely non-aqueous media, to give 5(x,6j8-diols. The main conclusions are summarized in last year s report. The opening of epoxides with acetonitrile and an acid has now been extended to a epoxide, predictably giving the 9a-acetamido-lljS-alcohols (see also Part II, Chap. 2, p. 365). " ... 

The addition of phenylselenide to oxaspiropentanes is highly accelerated by protic solvents which protonate and weaken the C-O bond, thus increasing its tendency toward nucleophilic attack. Furthermore, the epoxide opening by selenide is stereospecific and the stereochemistry obtained is opposite to that normally produced by the acid-catalysed rearrangement of oxaspiropentane (see equation 87). The selenoxide seems to play the role... 

Brill and co-workers used levoglucosane as a rigid scaffold to synthesise libraries both in solution [74] and solid phase [75]. The opening of epoxide 125 by different hydroxycarboxylic acid methyl esters catalysed by Lewis acid, followed by simultaneous new epoxide formation and ester hydrolysis gave the resulting free acid ready for attachment to the solid support. Epoxide opening reactions with alkoxides, amines and thiols were carried out on solid phase... 

Cyclohexene oxide 236 is opened with benzoic acid catalysed by 2.5% of the cobalt salen complex 235 to give the asymmetric half ester 237. Although the ee is only 75% this is improved by recrystallisation to 98% ee. Epoxides on other ring sizes can also be opened enantioselectively. 

Acid-catalysed opening of aziridines is usually quite rapid, but simple nucleophilic reactions, without acid catalysis, are very slow, due to the much poorer leaving ability of negatively charged nitrogen, however A-acyl- or A-sulfonyl-aziridines have reactivity similar to epoxides ... 

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