Oxacyclopropane , from

Reactions with sulfur ylides proceed differently. The products are oxacyclo-propanes (oxiranes) —not alkenes. The addition step proceeds as with the phosphorus ylides, but the negatively charged oxygen of the dipolar adduct then displaces the sulfonium group as a neutral sulfide. This is an intramolecular Sn2 reaction similar to the formation of oxacyclopropanes from vicinal chloroalcohols (Section 15-11C) ... 

Oxacyclopropane (oxirane), the simplest cyclic ether, is an outstanding exception to the generalization that most ethers are resistant to cleavage. Like cyclopropane, the three-membered ring is highly strained and readily opens under mild conditions. Indeed, the importance of oxacyclopropane as an industrial chemical lies in its readiness to form other important compounds. The major products derived from it are shown in Figure 15-5. 

Oxacyclopropanes also can be prepared from vicinal chloro- or bromo-alcohols and a base. This is an internal SN2 reaction and, if the stereochemistry is correct, proceeds quite rapidly, even if a strained ring is formed ... 

Acidic conditions also can be used for the cleavage of oxacyclopropane rings. An oxonium ion is formed first, which subsequently is attacked by the nucleophile in an SN2 displacement or forms a carbocation in an SN1 reaction. Evidence for the SN2 mechanism, which produces inversion, comes not only from the stereochemistry but also from the fact that the rate is dependent on the concentration of the nucleophile. An example is ring opening with hydrogen... 

Some acid-catalyzed solvolysis reactions of oxacyclopropanes appear to proceed by SN1 mechanisms involving carbocation intermediates. Evidence for the SN1 mechanism is available from the reactions of unsymmetrically substituted oxacyclopropanes. For example, we would expect the conjugate acid of 2,2-dimethyloxacyclopropane to be attacked by methanol at the primary carbon by an SN2 reaction and at the tertiary carbon by an SN1 reaction ... 

The grouping C—O—C—O—C is characteristic of an acetal or a ketal (see Section 15-4E), but it also can be regarded as an ether with two ether links to one carbon. Compared to other ethers (except for the oxacyclopropanes), substances with the C—O—C—O—C group are very active toward acidic reagents, as pointed out in connection with their formation from alcohols (Section 15-4E) and their use as protecting groups for the OH function (Section 15-9C). 

If you iinagine that the oxacyclopropane was made from an alkene, then the final product contains an alcohol and an R group attached to each end of the original double bond, just what you want. Apply this approach here, using the oxacyclopropane derived from cyclohexene ... 

What remains is to identify compound B, which gives an oxacyclopropane stereoisomeric to that formed from compound A, but at a slower rate, and D, which gives the same product as C, but also more slowly. Because both types of reactions under consideration require an axial leaving group, it makes sense to flip the chairs of the remaining starting compounds (in which the —Br is currently equatorial) and see what we get. 

B Oxacyclopropane formation from a C=C double bond MCPBA or any other peroxycarboxylic acid may be used. 

The final phenol probably arises from reversal of the last two steps. The oxacyclopropane ring can always close again, but eventually the carbocation reacts via an alternative pathway, involving D migration to give the rearranged aromatic product. 

The ring-opening process of Equation 8.45 is, of course, simply the reverse of the process by which oxiranes (oxacyclopropanes, epoxides) are formed from halohy-drins (e.g., see item 3,Table 7.6). Further, as written, the processes shown in Schemes 8.90-8.92 are reversible and thus, at least in principle, carbonyl compounds can be converted to enol ethers, acetals (and ketals), and orthoesters. However, while acetals and ketals readily form from alcohols and acids under dehydrating conditions (Chapter 9) and esters undergo exchange reactions with alcohols in the... 

If, in place of water, the acid with the non-nucleophilic gegenion is added to a methyl alcohol solution of oxirane (ethylene oxide, oxacyclopropane), methyl cel-losolve [CH3OCH2CH2OH] is formed and addition of a second equivalent of ethylene oxide (oxirane, oxacyclopropane) yields CH3OCH2CH2OCH2CH2OH, methyl carbitol. Families of carbitols and cellosolves, resulting from the use of alcohols other than methanol, are common, high-boiling industrial solvents. 

As anticipated by the formation of oxiranes (oxacyclopropanes, epoxides) from halohydrins, the four-membered oxygen-containing ring, oxetane (oxacyclobutane), can be prepared by heating 3-chloropropanol (HOCH2CH2CH2CI) with potassium hydroxide (KOH) (Equation 8.51). 

The first thing to do is write the structure of 3-hexanol. Then look to see how many pathways lead to this structure from oxacyclopropanes and examine each path for feasibility. 

We recognize two possible retrosynthetic paths to 3-hexanol from oxacyclopropanes removal of an anti H with simultaneous ring closure either to the left side or the right side. In our drawing, these two pathways are indicated by a and b, respectively. 

Oxacyclopropane Formation from an Alkene Through the Haloalcohol... 

Outline a short synthesis of tra s-2-methylcyclohexanol from cyclohexene. (Hint Review the reactions of oxacyclopropanes in Section 9-9.)... 

Alkynes can also be prepared from other alkynes. The reaction of terminal alkynyl anions with alkylating agents, snch as primary haloalkanes, oxacyclopropanes, aldehydes, or ketones, results in carbon-carbon bond formation. As we know (Section 13-2), such anions are readily prepared from terminal alkynes by deprotonation with strong bases (mostly alkyllithium reagents, sodinm amide in liqnid ammonia, or (jrignard reagents). Alkylation... 

In Summary Alkynes can be prepared from other alkynes by alkylation with primary haloalkanes, oxacyclopropanes, or carbonyl compounds. Ethyne itself can be alkylated in a series of steps. 

Intermediate E can be approached by using nucleophihc cyanide in a different manner—namely, by attack at the less hindered position of phenyloxacyclopropane. The latter would arise from phenyl-ethene (styrene) by oxacyclopropanation (Section 12-10), and phenylethene could in turn be readily made from acetylbenzene by reduction-dehydration. 

Epoxides are reactive entities due to the strain of the oxacyclopropane moiety. They can be formed from a variety of precursors but this chapter will be limited to the formation of epoxides by the oxidation of double bonds. If the double bond bears three or four different substitutes, epoxidation creates one or two chiral centers. In almost all epoxide-containing natural products these chiral centers were not created by chance and the products are nonracemic but contain an excess of one enantiomer. The chirality of the epoxides is caused by the chirality and the regioselectivity of the forming enzyme. This is a general attribute of enzymes making them ideal tools for enantiopure syntheses. 

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