Protonated epoxide

The cleavage reaction occurs in three steps O protonation of the epoxide, Sn2 nucleophilic attack on the protonated epoxide, and deprotonation of the ring-opened product. Draw the complete mechanism. How many intermediates are there Which step determines diol stereochemistry ... 

With weak nucleophiles such as methanol, and in the presence of acid, the reaction proceeds via nucleophilic attack on the protonated epoxide. Examine the LUMO of protonatedpropylene oxide. Does this properly identify the site for nucleophilic attack which will lead to the observed product (Hint The most accessible parts of the LUMO are best identified by simultaneously displaying the molecule as a space-filling model and the LUMO as a mesh surface.)... 

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. 

Evidently, the transition state for acid-catalyzed epoxide opening has an Sn2 -like geometry but also has a large amount of S]v-l-like carbocationic character- Since the positive charge in the protonated epoxide is shared by the more highly substituted carbon atom, backside attack of Br- occurs at the more highly substituted site. 

Steps 1-2 of Figure 27.14 Epoxide Opening and Initial Cyclizations Cyclization is initiated in step 1 by protonation of the epoxide ring by an aspartic acid residue in the enzyme. Nucleophilic opening of the protonated epoxide by the nearby 5,10 double bond (steroid numbering Section 27.6) then yields a tertiary carbo-cation at CIO. Further addition of CIO to the 8,9 double bond in step 2 next gives a bicyclic tertiary cation at C8. 

Another circumstance that increases leaving-group power is ring strain. Ordinary ethers do not cleave at all and protonated ethers only under strenuous conditions, but epoxides are cleaved quite easily and protonated epoxides even more easily. Aziridines and episulfides, three-membered rings containing, respectively, nitrogen and sulfur, are also easily cleaved (see p. 458). ... 

Substitution of the free epoxide, which generally occurs under basic or neutral conditions, usually involves an Sn2 mechanism. Since primary substrates undergo Sn2 attack more readily than secondary, unsymmetrical epoxides are attacked in neutral or basic solution at the less highly substituted carbon, and stereospecifically, with inversion at that carbon. Under acidic conditions, it is the protonated epoxide that undergoes the reaction. Under these conditions the mechanism can be either SnI or Sn2. In S l mechanisms, which favor tertiary carbons, we might expect that attack would be at the more highly substituted carbon, and this is indeed the case. However, even when protonated epoxides react by the 8 2 mechanism, attack is... 

Some such pathway is necessary to account for the migration of oxygen that is found. It may involve a protonated epoxide, a 1,2-diol, or simply a 1,2 shift of an OH group. 

This proton transfer step produces an intermediate that is very similar to a bromo-nium ion (a three-membered ring with a positive charge on an electronegative atom). Just as a bromonium ion can be attacked by water, similarly, a protonated epoxide can also be attacked by water ... 

The acid reacts with the epoxide to produce a protonated epoxide. 

The protonated epoxide reacts with the weak nucleophile (water) to form a protonated glycol, which then transfers a proton to a molecule of water to form the... 

Water acting as a nucleophile attacks the protonated epoxide from the side opposite the epoxide group. 

Reactivity of protonated epoxide. There is believed to be a zone of intermediate epoxide reactivity that is optimum for initiating the carcinogenic process [57-59], The molecule must be able to undergo the necessary reactions, yet not be so active it will interact prematurely with other cellular species. 

Abstract In the first part of this mini review a variety of efficient asymmetric catalysis using heterobime-tallic complexes is discussed. Since these complexes function at the same time as both a Lewis acid and a Bronsted base, similar to enzymes, they make possible many catalytic asymmetric reactions such as nitroal-dol, aldol, Michael, Michael-aldol, hydrophosphonyla-tion, hydrophosphination, protonation, epoxide opening, Diels-Alder and epoxi-dation reaction of a, 3-unsaturated ketones. In the second part catalytic asymmetric reactions such as cya-nosilylations of aldehydes... 

Model computational studies aimed at understanding structure-reactivity relationships and substituent effects on carbocation stability for aza-PAHs derivatives were performed by density functional theory (DFT). Comparisons were made with the biological activity data when available. Protonation of the epoxides and diol epoxides, and subsequent epoxide ring opening reactions were analyzed for several families of compounds. Bay-region carbocations were formed via the O-protonated epoxides in barrierless processes. Relative carbocation stabilities were determined in the gas phase and in water as solvent (by the PCM method). 

The protonated epoxides, i.e. the oxonium ions, could not be characterized as minima on the respective potential energy surfaces, as in every case the epoxide ring opened by a barrierless process upon O-protonation. Charge delocalization maps are shown in Figure 9, and some selected NPA-derived charges for the carbocations are displayed in Table 4. 

The protonated epoxide can also react with nucleophilic solvents such as CH3OH. 

In acid the protonated epoxide may undergo ring-opening to give an intermediate carbocation. 

When the protonated epoxide undergoes ring-opening, the CH,OH molecule attacks from the backside of the C. The nearby, newly formed OH group hasn t moved out of the way and blocks approach from the frontside. This leads to inversion at the chiral carbon. Since there was no change in group priorities, the configuration in the product is (S). 

Similar results have been obtained in the reactions of 1 and sodium salts of p-cresol and - and /J-naphthols. Under SN2 conditions (DMF or DMSO solvent), the alkylation of sodium cresolate occurs exclusively at the oxygen atom. The addition of a protic solvent causes C-alkylation, though the yields of C-alkylated products are low. Thus in acetone-water or dioxane-water, the yield of C-alkylated products 251 and 252 increases only up to 2%. C-Alkylation has also been observed in the reactions catalyzed by trifluoroacetic acid or boron trifluoride etherate at room temperature. The observed C-alkylation in protic media may be a reflection of a mechanism that involves a protonated epoxide or a more polarized transition state than in an SN2 pathway. 

Large negative p+ value consistent with formation of positive charge on the benzylic carbon. Thus epoxide ring opening (of protonated epoxide) is the rate-determining step. 

Acid-catalyzed nucleophilic ring opening proceeds by attack of methanol at the more substituted carbon of the protonated epoxide. Inversion of configuration is observed at the site of attack. The correct product is compound A. 

Our calculations have shown that an electron-withdrawing substituent increases the reactivity of a protonated epoxide by weakening the adjacent C—O bond107, accordingly, the chlorine in vinyl chloride has a positive effect with regard to factor (c) above. On the other hand, since the epoxidation of the olefin occurs by reaction with an electrophilic form of... 

The bromonium ion resembles a protonated epoxide (see Section 10.10) in both structure and reactions. Therefore, when the nucleophilic bromide attacks to open the three-membered ring, it approaches from the side opposite the other bromine. 

The crucial step is a back-side attack by the solvent on the protonated epoxide. Step 1 Protonation of the epoxide activates it toward nucleophilic attack. 

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