Oxygen epoxide opening

The mechanisms of these acid-catalyzed epoxide openings are more complex than they at first appear. They seem to be neither purely SN1 nor SN2 but instead to be midway between the two extremes and to have characteristics of both. Take the reaction of 1,2-epoxy-l-methylcyclohexane with HBr shown in Figure 18.2, for instance. The reaction yields only a single stereoisomer of 2-bromo-2-methyl-cyclohexanol in which the —Br and —OH groups are trans, an S 2-li.ke result caused by backside displacement of the epoxide oxygen. But the fact that Br attacks the more hindered tertiary side of the epoxide rather than the less hindered secondary side is an SN1 -like result in which the more stable, tertiary carbocation is involved. 

A limitation of epoxide deoxygenation with functionalized substrates became apparent in the second case where a mixture of olefins was isolated. Thus, the regioselectivity of epoxide opening and elimination of the titanium oxygen species was too low for practical use. 

Snapper and Hoveyda reported a catalytic enantioselective Strecker reaction of aldimines using peptide-based chiral titanium complex [Eq. (13.11)]. Rapid and combinatorial tuning of the catalyst structure is possible in their approach. Based on kinetic studies, bifunctional transition state model 24 was proposed, in which titanium acts as a Lewis acid to activate an imine and an amide carbonyl oxygen acts as a Bronsted base to deprotonate HCN. Related catalyst is also effective in an enantioselective epoxide opening by cyanide "... 

Silylation followed by selenium dioxide oxidation converted 13 into 14. Epoxidation of the derived TES ether proceeded by addition of oxygen to the more open face of the alkene, leading to 15. Ozonolysis followed by diastereoselective one-carbon homologation provided 17. This set the stage for intramolecular epoxide opening by the carboxylate, to give 2, in which all of the stereogenic centers of tetrodotoxin have been established. 

The proposed mechanism of the isomerization of polyfluorooxiranes to ketones does not involve a 1,2-fluorine shift, but rather coordination of the Lewis acid with the epoxide oxygen, ring opening to the carbocation, and intermolecular addition and elimination of fluoride.29 45... 

The indirect electron transfer sensitization reported earlier when biphenyl was present in dicyanoanthracene-sensitized epoxide openings also finds analogy in the sensitized oxygenation of a mixture of trans-stilbene and tetraphenylethylene, eq. 76 (233) ... 

In the case of 1,4-dimethylbenzene epoxide (181), incursion of intermediates like l,4-dimethyl-l,4-dihydroxydihydrobenzene (182)91,92 or intermediates like 4,8- and 4,5-indane oxides (183 and 184), respectively, by oxygen walk8,93-96 does not allow prediction of the product of epoxide opening on... 

Ring-opening chemistry is characteristic of oxygen heterocycles too, and there is no need for us to revisit epoxide opening here. 

Some noteworthy intramolecular nucleophilic ring openings have been reported in the recent literature, which can be used to prepare functionalized heterocycles of synthetic interest. For example, the highly oxygenated epoxide 100 undergoes rearrangement induced by boron trifluoride etherate, whereby anchimeric assistance from the pendant phenylthio substituent leads to an intermediate episulfonium ion 101 which subsequently suffers 5-e o-tet cyclization to form the tetrahydrofiiran derivative 102 <03TL5547>. 

Diols can be prepared by direct hydroxylation of an alkene with OSO4 followed by reduction with NaHSOs (Section 7.8). The reaction takes place readily and occurs with syn stereochemistry. We ll see in the next chapter that 1,2-diols can also be prepared by acid-catalyzed hydrolysis of epoxides—compounds with a three-membered, oxygen-containing ring. Epoxide opening is complementary to direct hydroxylation because it occurs with anti stereochemistry. 

Squalene oxide is protonated on oxygen, and the epoxide ring is opened by nucleophilic attack of the double bond six carbons away, to yield a six-membered, cyclic carbocation intermediate. This step is similar to the acid-catalyzed epoxide openings we saw in Section 18.8. 

Competition between an alkene and an ether oxygen for participation in epoxide opening is evident in the reactions of trichothecenes (illustrated by the skeletal structure 20 equation 8). In aqueous acid, participation of the ether oxygen is favored and (21) is formed, probably due to preferred cleavage at the tertiary center under the more electrophilic conditions. Under neutral or basic conditions, the diminished role of intermolecular electrophile (water) results in unusual scission of the primary epoxide bond, with formation of (22). ... 

While obviously natural enediynes 2-4 behave in the same way, in dynemicin the cascade of events is different. However, this molecule also displays a delivery unit (the anthraquinone), a safety catch (the epoxide) and a trigger (the quinone). Bioreduction of the quinone unleashes two lone pairs (one on the nitrogen and one on the upper hydroquinone oxygen) which bring about intramolecular epoxide opening. ... 

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