Heteroarenes electrophilic attack

The formation of six-membered or larger rings by intramolecular C-H bond insertion normally requires the attacked position to be especially activated towards electrophilic attack [1157,1158]. Electron-rich arenes or heteroarenes [1159-1162] and donor-substituted methylene groups can react intramolecularly with electrophilic carbene complexes to yield six- or seven-membered rings. Representative examples are given in Table 4.8. 

Electron-rich arenes and heteroarenes are known to react with alkynes in the presence of Pd or Pt catalysts in acidic solvents to give the corresponding alkenylated products. The reaction mechanism through C-H metallation and alkyne insertion, which is similar to path B in Scheme 18.82, was previously proposed [4]. However, mechanistic investigations conducted later suggested that this reaction may be initiated by the activation of alkynes rather than arenes by a catalyst, followed by electrophilic attack of formed cationic alkenyl species on arenes [87]. The observed trans-C-H bond addition across alkynes can be explained by this mechanism. These kinds of reactions as well as those involving alkyne activation by the Lewis acid catalysts have been summarized in comprehensive review articles [88]. 

A catalytic cycle shown above has been proposed. The reaction begins with the oxidation of the iron complex to form the oxo-iron species by reaction with oxygen. An electrophilic attack of this oxo-iron complex on C-2 position of heteroarenes is aided by the heteroatom. Following a consequential deprotonation, a tertiary complex comprising iron, heterocycle, and MCPA ligand is formed. With the introduction of arylboronic acid, transmetalation and then elimination of the iron complex can yield the desired product. 

To summarize, the reactivity of oxazoles closely resembles that of the ftirans, especially in their readiness to undergo ring-opening reactions and [4+2] cycloadditions. The pyridine-like N-atom impedes electrophilic substitution reactions. On the other hand, it facilitates the attack of nucleophiles onto the C-2 atom. Although oxazole is considered to be a heteroarene, because of its six delocalized ring electrons, its aromaticity is low and comparable to that of furan. 

Most reports concerning 2//-pyran-2-ones (a-pyrones) involve non-fluorinated derivatives, which perform important biological functions in nature and have unlimited synthetic potential for the construction of a variety of arenes and heteroarenes [28], However, very few deal with 2-pyrones containing fluoroalkyl groups. It is evident that the C-2, C-4 and C-6 positions of the 2-pyranone ring are electrophilic in nature and prone to nucleophilic attack. The presence of polyfluoroalkyl substituents on the pyrone ring favours these reactions. At the same time, R -containing 2-pyrones behave as cyclic dienes in cycloadditions. 

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