Aryl cations are electrophilic species can not be thermally generated in solution, but they are smoothly accessible under mild conditions through the photoheterolysis of electron-rich aryl halides (or esters, see Scheme below). [1]

The high reactivity of aryl cations towards different kinds of nucleophiles has been exploited by our research group for the metal-free photochemical formation of aryl-carbon bonds. [2] The Scheme below shows some significant examples of this synthetic strategy.

If ketene silyl acetals are used as nucleophiles (path a), the photochemical reaction leads efficiently to the corresponding α-aryl propionic acids. These are interesting molecules, since some compounds bearing this moiety are known as NSAIDs (NonSteroidal Anti-Inflammatory Drugs).

A variety of allyl anisoles and allyl phenols (naturally occurring bioactive compounds) has been obtained in nearly quantitative yields, by reaction of aryl cations with allyltrimethylsilane (path b).

A surprisingly clean reaction occurred upon reactions of substituted phenyl cations with terminal alkynes, where the corresponding aryl alkynes were isolated in 70-90% yield (path c). This process is actually an interesting metal-free alternative to the dimetallic-mediated (palladium and copper) Sonogashira reaction.

We likewise applied phenyl cation chemistry to the arylation of aromatics, such as benzene and symmetric methylbenzenes (path d). Thus, we obtained several asymmetric or crowded biaryls in high yields. Noteworthy, steric hindering caused no major limitation and the arylation was fully chemoselective.

π-Bond nucleophiles are not the only useful traps for aryl cations. For example, such electrophiles are highly reactive also towards inorganic anions, such as iodide and cyanide. The irradiation of aryl halides and esters in a water-acetonitrile solution of KCN afforded various benzonitriles, an important class of compounds which finds application among agrochemicals and pharmaceuticals (path e).

Recently, we have also proposed a new three-component reaction for the synthesis of aryl acetals and aryl ketals; this exploits the reaction of aryl cations with a vinyl ether followed by the addition of the alcoholic medium (path f).

Future developments

Our interest in phenyl cations chemistry is now focusing on the use of different precursors, including a variety of aromatic sulfonates. Moreover, we are pursuing the research for innovative synthetic procedures exploiting these highly reactive intermediates. [3,4]

References

1. Fagnoni, M.; Albini, A. “Arylation Reactions: The Photo-S_N1 Path via Phenyl Cation as an Alternative to Metal Catalysis” Acc. Chem. Res. 2005, 38, 713-721. DOI: 10.1021/ar0402356
2. Dichiarante, V.; Fagnoni, M. “Aryl Cation Chemistry as an Emerging Versatile Tool for Metal-Free Arylations” Synlett 2008, 787-800. DOI: 10.1055/s-2008-1042933
3. Raviola, C.; Protti, S.; Ravelli, D.; Mella, M.; Albini, A.; Fagnoni, M. “Acetalization Allows the Photoheterolysis of the Ar–Cl Bond in Chlorobenzaldehydes and Chloroacetophenones” J. Org. Chem. 2012, 77, 9094–9101. DOI: 10.1021/jo3016264
4. Protti, S.; Fagnoni, M.; Albini, A. “A Photochemical Route to 2-Substituted Benzo[b]furans” J. Org. Chem. 2012, 77, 6473-6479. DOI: 10.1021/jo3010183