Dicationic electrophiles

Changing the emphasis to synthetic chemistry in superacid media, in Chapter 8, D. Klumpp examines the chemistry of dicationic electrophiles, demonstrating their enhanced reactivity via heteroatom protonation. In Chapter 9, S. Ito et al. explore the potential utility of stabilized carbocations for designing redox-active chromophores. 

Much of our research has involved the use of dicationic electrophiles in reactions with very weak nucleophiles, such as non-activated arenes and alkanes. By comparison to similar monocationic electrophiles, we have been able to show the extent of electrophilic activation by adjacent cationic centers. For example, carbocations show an increased reactivity with a nearby cationic charge (eqs 3-4).9 When 1,1-diphenyletheneis reacted with superacidic CF3SO3H... 

In summary, we have shown that stable cationic charge centers can significantly enhance the reactivities of adjacent electrophilic centers. Most of the studied systems involve reactive dicationic electrophiles. A number of the reactive dications have been directly observed by low temperature NMR. Along with their clear structural similarities to superelectrophiles, these dicationic systems are likewise capable of reacting with very weak nucleophiles. Utilization of these reactive intermediates has led to the development of several new synthetic methodologies, while studies of their reactivities have revealed interesting structure-activity relationships. Based on the results from our work and that of others, it seems likely that similar modes of activation will be discovered in biochemical systems (perhaps in biocatalytic roles) in the years to come. 

Zhang, Y. Aguirre, S. A. Klumpp, D. A. Reactive, Dicationic Electrophiles Electrophilic Activation Involving the Phosphonium Group. Tetrahedron Lett. 2002, 43, 6837-6840. 

Superacid-catalysed intramolecular reactions of some dicationic electrophiles have been investigated.36 The positively charged centres migrate apart and this chemistry gives a new synthetic route to aza-polycyclic compounds. The polycyclic compound (26) can, for example, be formed from reaction of 2-phenyl-3-(l-hydroxy-2-phenyl-ethyl)quinoline (25) with CF3SO3H at 25 °C, loss of water and benzene being involved. Highly diastereoselective polycyclization of homo(polyprenyl)arenes [e.g. (27)... 

In a study involving the superacid-catalyzed reaction of amino-alcohols, a chiral, dicationic electrophile was observed by low temperature 13C NMR.31 Ionization of benzylic alcohols in superacids can generate stable carbocations, such as the trityl cation. Because of the resonance stabilization of the carbocationic centers, they are fairly weak electrophiles, incapable of reacting with benzene (eq 31). However, it was shown that adjacent ammonium groups can increase the electrophilic reactivities of the diphenylethyl cations (eq 32). 

When the amino alcohol (56) is ionized in FSO3H-SbFs -SCFCIF at —40°C, a clean NMR spectrum is observed for the reactive dicationic electrophile (57, Figure 2), showing the carbocationic resonance at < 13C 211.5. 

A series of phosphonium-carboxonium dications have also been studied in superacid catalyzed reactions.313 When the dicationic electrophiles are compared with similar monocationic species, it is clear that the phos-phonium group enhances the electrophilic character of the carboxonium center. For example, protonated acetone is incapable of reacting with benzene in condensation reactions, however, the phosphonium-substituted carboxonium ion (124) reacts in high yield (eq 40). 

Initial ionization gives an ammonium-carboxonium dication, which then produces the ammonium-carbenium dication (230). A variety of dicationic electrophiles like 230 have been proposed. 

Phenylethyl-substituted pyridinecarboxaldehydes (69) were shown to generate dicationic electrophiles such as the dicationic carboxonium ion (70)." ° These undergo cyclization to the dicationic carbocation (71), which may be trapped by arenes or water. The chemistry provides a useful route to triarylmethanes or 10,ll-dihydro-5//-benzo[4,5]cyclohepta[l,2-( ]pyridin-5-ones. 

Li A, Kindelin PJ, Klumpp DA (2006) Charge migration in dicationic electrophiles and its application to the synthesis of aza-polycycUc aromatic compounds. Org Lett 8 1233-1236... 

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