Sean P. McClintock

Synthesis of α-Ketoester- and α-Hydroxyester-Substituted Isoindazoles via the Thermodynamic Coarctate Cyclization of Ester-Terminated Azo-Ene-Yne Systems

The synthesis of isoindazoles bearing alpha-ketoester and alpha-hydroxyester groups via the coarctate cyclization of ester-terminated azo-ene-yne precursors is described. Whereas previous studies on isoindazole formation have shown the reaction to proceed through a kinetic coarctate pathway, functionalization of the terminal acetylene with a methyl ester sufficiently stabilizes the carbene intermediate to make the coarctate cyclization the thermodynamic pathway. Density functional theory (DFT) computations reveal ca. 8-9 kcal mol(-1) lower energy transition states for the coarctate pathway compared to the parent system.

Coarctate versus pericyclic reactivity in naphthalene-fused azo-ene-ynes: synthesis of benzocinnolines and benzoisoindazoles.

The cyclization reactions of naphthalene-fused azo-ene-yne compounds are explored both computationally and experimentally. Calculations reveal that naphtho-fusion to an azo-ene-yne scaffold does not significantly alter the transition state energies compared to the benzene-based systems; however, fusing the naphthalene in an angular fashion leads to lower energy intermediates due to the creation of arenes possessing greater aromaticity. Experimentally, the cyclization of the angular systems yields not only the expected monomeric benzocinnolines and benzoisoindazoles, but also several dimeric structures, including one that readily isomerizes in the presence of light and/or trace acid.

Computational analysis on the dual reactivity of conjugated "ene-ene-yne" systems.

The design of new reactions that yield benzo-fused five- or six-membered rings arising from conjugated ene-ene-yne precursors was examined computationally. Inclusion of heteroatoms (particularly N) in the bond making position was shown to lower activation energies due to participation of the lone pair electrons in the cyclization reactions. By systematically varying the atomic configuration in the ene-ene-yne system, the influence of heteroatoms was used to identify optimal candidates for future experimental study.

Synthesis of 1-Substituted Benzo[c]isoxazol-3(1H)-imines via Tandem Nitroso-Ene/Intramolecular Cyclizations of 2-Nitrosobenzonitrile

Instead of reacting via the expected coarctate cyclization pathway, 2-nitrosobenzonitrile undergoes a tandem nitroso-ene/intramolecular cyclization to form benzo[c]isoxazol-3(1H)-imines in very good yields under neutral conditions and at moderate temperatures. Treatment of three of the imines with HBF4 results in dimerization/condensation to furnish unusual, delocalized cationic systems.

Dications of 3-Phenyl-indenylidene Dibenzo[a.d]cycloheptene: The Role of Charge in the Antiaromaticity of Cationic Systems

Dications of 9-(3-phenyl-1H-inden-1-ylidene)-5H-dibenzo[a,d]cycloheptene, 5(2+), were prepared by oxidation with SbF(5) in SO(2)ClF, and their magnetic behavior was compared to dications of 9-(3-phenyl-1H-inden-1-ylidene)-9H-fluorene, 2(2+). The good correlation between the experimental (1)H NMR shifts for the dications that were oxidized cleanly and the chemical shifts calculated by the GAIO method supported the use of the nucleus independent chemical shifts, NICS, to evaluate the antiaromaticity of the indenyl systems of 2(2+)/5(2+) and their unsubstituted parent compounds, 6(2+) and 7(2+), as well as the antiaromaticity of the fluorenyl system of 2(2+)/7(2+) and the aromaticity of the dibenzotropylium system of 5(2+)/6(2+). Antiaromaticity was shown to be directly related to the amount of charge in the antiaromatic systems, with the antiaromatic systems more responsive to changes in the calculated NBO charge than the aromatic systems. The antiaromaticity was also shown to be directly related to the amount of delocalization in the ring system. The aromaticity of the dibenzotropylium system was much less responsive to changes in the amount of charge in the tropylium system, because the aromatic system was much more completely delocalized. Thus, antiaromatic species are more sensitive probes of delocalization than aromatic ones.

Magic Acid Free Generation of Antiaromatic Dications at Room Temperature

A new method for the generation of dicationic species via ionization of diols is described. The method makes use of milder reagents at room temperatures, an advantage over use of Magic Acid at -78 °C. A series of mono- and dications were synthesized successfully, including previously unattainable species.