Electrophilic Attack on Ring Oxygen

Molecular orbital calculations predict that oxirane forms the cyclic conjugate acid (39), which is 30 kJ moF stabler than the open carbocation (40) and must surmount a barrier of 105kJmoF to isomerize to (40) (78MI50500). The proton affinity of oxirane was calculated (78JA1398) to be 807 kJ mol (cf. the experimental values of 773 kJ moF for oxirane and 777-823 kJ moF for dimethyl ether (80MI50503)). The basicity of cyclic ethers is discussed in (B-67MI50504). 

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Nucleophilic attack on ring carbon (Scheme 39) is the most important reaction of these compounds (the electrophile may bond to oxygen either before or after nucleophilic attack). For vinylogous nucleophilic opening by 5n2 attack on ethenyloxiranes see Section 5.5.3.8. 

This is a widely observed type of reaction for oxetanes and 2-oxetanones and has many variations. The typical pattern involves electrophilic attack on the ring oxygen atom of oxetanes to form an unstable oxetanium ion. The latter either undergoes C—O ring scission to a carbonium ion which then combines with a nucleophile, or nucleophilic attack by even very weak nucleophiles at the a-carbon atom. For clarity, these reactions will be arranged according to the nature of the overall process. 

The Friedel-Crafts alkylation of aromatic compounds by oxetanes in the presence of aluminum chloride is mechanistically similar to the solvolyses above, since the first step is electrophilic attack on the ring oxygen by aluminum chloride, followed by a nucleophilic attack on an a-carbon atom by the aromatic compound present. The reaction of 2-methyloxetane and 2-phenyloxetane with benzene, toluene and mesitylene gave 3-aryl-3 -methyl-1-propanols and 3-aryl-3-phenyl-l-propanols as the main products and in good yields (equation 27). Minor amounts of 3-chloro-l-butanol and 4-chloro-2-butanol are formed as by-products from 2-methyloxetane, and of 3-phenyl-l-propanol from 2-phenyloxetane (73ACS3944). 

Attempted annulation of 3-iodoflavones, for example 428, by internal alkynes catalyzed by Pd(OAc)2 in the presence of NaOAc and LiCl yielded a mixture of two compounds (Scheme 73) <1998JOC2002>. While the expected benzoxanthenes (e.g., 429) were isolated as the minor compound, tetrasubstituted furans (e.g., 430) resulting from the electrophilic attack on the carbonyl oxygen atom by the vinylpalladium intermediate followed by pyrone ring opening were the major product. 

These substrates, studied exclusively by Conia, are a hybrid in that they contain all of the requisite carbon atoms for the ring but still require a coupling reaction. The action of hot poiyphosphoric acid on alkenic esters (77) may begin by cracking the alkyl carbon-oxygen bond to produce an alkene and the parent acid. This new composition is in principle identical to the Dev mixture just described, and likely proceeds similarly by acylium ion generation and electrophilic attack on the in situ generated alkene (equation 42). 

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