Oxacyclopropanes nucleophilic ring opening

Although ordinary ethers are relatively inert, the strained structure of the oxacyclopropanes makes possible nucleophilic ring-opening reactions. This section presents details of these processes. 

Nucleophilic ring opening of oxacyclopropanes by n2 is regioselective and stereospecihc... 

Nucleophilic Ring Opening of an Unsymmetrically Substituted Oxacyclopropane... 

The only way to obtain a product with two CH3 groups attached to the same carbon is to have the methyl group of CHsLi add to the carbon of the oxacyclopropane that already contains one CH3. Therefore, the observed minor product is the result of nucleophilic ring opening of the starting compound by attack at the more hindered position, usually neglected because it is less favored. 

How can this be explained The situation is very similar to the acid-catalyzed nucleophilic ring opening of oxacyclopropanes (Section 9-9), in which the intermediate contains a protonated oxygen in the three-membered ring. In both reactions, the nucleophile attacks the more highly substituted carbon of the ring, because this carbon is more positively polarized than the other. 

As illustrated by the chemistry of the oxacyclopropanes (Section 9-9), ring strain allows the three- and four-membered heterocycles to undergo nucleophilic ring opening readily. In contrast, the larger, unstrained systems are relatively inert to attack. 

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... 

Look at AlClj as a Lewis acid and benzene as a nucleophile. Recall (.Section 9-0) that acid-catalyzed ring openings of oxacyclopropanes give Sul regio-chemistry (most stable carbocation) but Sn2 stereochemistry (backside nucleophilic attack). So. 

Since you are not told otherwise, assume a racemic mixture for the (chiral) oxacyclopropane starting material. Write out the answer for one enantiomer then indicate that the product is racemic. The two carbons of the oxacyclopropane are equivalent (rotate a model of the molecule 180° about a vertical axis to prove this to yourself), so it makes no difference which of the two carbons you attack with the nucleophilic carbon of the lithium reagent. This is ring-opening under basic conditions and follows an SN2 mechanism with inversion at the site of nucleophilic attack (Section 9-9). 

Oxacyclopropane is subject to bimolecular ring opening by anionic nucleophiles. Because of the symmetry of the substrate, substimtion occurs to the same extent at either carbon. The reaction proceeds by nucleophilic attack, with the ether oxygen functioning as an intramolecular leaving group. 

Ring opening of oxacyclopropanes is also catalyzed by acids. The reaction in this case proceeds through initial cyclic alkyloxonium ion formation followed by ring opening as a result of nucleophilic attack. 

Why do we not simply write the isomeric free carbocations as intermediates in the acid-catalyzed ring openings The reason is that the cyclic oxonium ion has an octet sfructure, whereas the carbocation isomer has a carbon with an electron sextet. Indeed, experimentally, inversion is observed when reaction takes place at a stereocenter. Like the reaction of oxacyclopropanes with anionic nucleophiles, the acid-catalyzed process includes backside displacement—in this case, on a highly polarized cyclic alkyloxonium ion. 

Whereas nucleophihc ring opening of oxacyclopropanes by anions is at the less substituted ring carbon according to the rules of the 5 2 reaction, acid-catalyzed opening favors the more substituted carbon, because of charge control of nucleophilic attack. 

In Summary Halonium ions are subject to stereospeciflc and regioselective ring opening in a manner that is mechanistically very similar to the nucleophilic opening of protonated oxacyclopropanes. Halonium ions can be trapped by halide ions, water, or alcohols to give vicinal dihaloalkanes, haloalcohols, or haloethers, respectively. The principle of electrophilic additions can be applied to any reagent A-B containing a polarized or polarizable bond. 

Treatment of oxacyclopropanes with water in the presence of catalytic acid or base leads to ring opening to the corresponding vicinal diols. These reactions follow the mechanisms described in Section 9-9 The nucleophile (water or hydroxide) attacks the side opposite the oxygen in the three-membered ring, so the net result of the oxidation-hydrolysis sequence constitutes an anti dihydroxylation of an alkene. In this way, tram-2-butene gives me50-2,3-butanediol, whereas ds-2-butene furnishes the racemic mixture of the 1R, >R and 2S,3S enantiomers. 

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