Douglas A. Klumpp

Superelectrophiles and their chemistry

Preface. 1. General Aspects. 2. Study of Superelectrophiles. 3. Generating Superelectrophiles. 4. Gitonic Geminal Superelectrophiles. 5. Gitonic Vicinal Superelectrophiles. 6. Gitonic 1,3-Superelectrophiles. 7. Distonic Superelectrophiles. 8. Significance and Outlook. Index.

Superacid-Promoted Reactions of α-Ketoamides and Related Systems

The superacid-promoted reactions of alpha-hydroxy and alpha-ketoamides have been studied. Ionization of these compounds leads to varied aryl-substituted oxyindole products. In some cases, electrocyclization can lead to substituted fluorene products. Dicationic, superelectrophilic intermediates are proposed as intermediates leading to the products from alpha-hydroxy and alpha-ketoamides.

Superelectrophiles and the Effects of Trifluoromethyl Substituents

Trifluoromethyl-substituted superelectrophiles were generated in superacid (CF(3)SO(3)H), and their chemistry was examined. The strong electron-withdrawing properties of the trifluoromethyl group are found to enhance the electrophilic character at cationic sites in superelectrophiles. This leads to greater positive-charge delocalization in the superelectrophiles. These effects are manifested by the unusual chemo-, regio-, and stereoselectivities shown by the superelectrophiles in chemical reactions.

Charge delocalization and enhanced acidity in tricationic superelectrophiles.

This Article presents the results from studies related to the chemistry of tricationic superelectrophiles. A series of triaryl methanols were ionized in Brønsted superacids, and the corresponding tricationic intermediates were formed. The trications are found to participate in two types of reactions; both are characteristic of highly charged organic cations. One set of reactions occurs through charge migration. A second set of reactions occurs through deprotonation of an unusually acidic site on the tricationic species. One of the tricationic intermediates has been directly observed by low temperature NMR spectroscopy. These highly charged ions and their reactions have also been studied using density functional theory calculations. As a result of charge migration, electron density at a carbocation site is found to increase with progression from monocationic to pentacationic structures.

Superacid-promoted additions involving vinyl-substituted pyrimidines, quinoxalines, and quinazolines: mechanisms correlated to charge distributions.

The superacid-promoted reactions of vinyl-substituted N-heterocycles have been studied. Diprotonated pyrimidines, quinoxalines, and quinazolines exhibit an unusual regioelectronic effect that controls the type of addition reaction observed. Depending on the ring position of the vinyl substituent, either conjugate addition or Markovnikov addition occurs. The mode of addition has been shown to correlate well to NBO calculated charges.

Preparation of aza-polycyclic aromatic compounds via superelectrophilic cyclizations.

Alkenyl-substituted N-heterocycles react in superacidic CF3SO3H (triflic acid) to produce dicationic intermediates. These superelectrophiles undergo cyclizations to give varied aza-polycyclic aromatic compounds in generally good yields (27-99%, 16 examples). Theoretical calculations indicate a preference for charge-separated dicationic intermediates.

Friedel-Crafts Acylation with Amides

Friedel-Crafts acylation has been known since the 1870s, and it is an important organic synthetic reaction leading to aromatic ketone products. Friedel-Crafts acylation is usually performed with carboxylic acid chlorides or anhydrides, while amides are generally not useful substrates in these reactions. Despite being the least reactive carboxylic acid derivative, we have found a series of amides capable of providing aromatic ketones in good yields (55-96%, 17 examples). We propose a mechanism involving diminished C-N resonance through superelectrophilic activation and subsequent cleavage to acyl cations.

Protolytic defluorination of trifluoromethyl-substituted arenes

A series of trifluoromethyl-substituted arenes were studied in their reactions with Brønsted superacids. The products from these reactions suggest the formation of reactive electrophiles, such as carbocations, acylium cations or equivalent electrophilic species. As such, Friedel-Crafts-type reactions occur between these species and arene nucleophiles. NMR studies were done, and the results suggest the formation of an acyl group from the trifluoromethyl groups in the superacid.

Superelectrophilic Chemistry of Imidazoles

The mechanistic and synthetic chemistry of imidazole-based superelectrophiles has been studied. The protonated imidazole ring, or imidazolium group, is shown to enhance the electrophilic reactivity of an adjacent carboxonium group (compared to a related monocationic species). This leads to efficient condensation reactions between imidazole aldehydes and ketone with arenes in the Brønsted superacid CF3SO3H. The imidazole-based superelectrophiles are shown to be useful in other reactions leading to functionalized heterocycles. The imidazolium group may also trigger charge migration reactions in dicationic species.

Superelectrophiles: Charge–Charge Repulsive Effects

Over the years, a significant number of di- and tricationic superelectrophiles have been studied. Many of these superelectrophiles exhibit charge-charge repulsive effects due to the interaction of the positive charges. Charge-charge repulsion can lead to novel molecular rearrangements, profoundly influence reactivities, and may significantly effect molecular structure.