Highest occupied molecular orbital regioselectivity

The regioselectivity associated with the nitration of the 7-bromo-l,5-benzodiazepinone 9, which occurred at C-8 and C-9, was examined by considering the relative atomic charge densities, total pz electron population, and the electron population density of the highest occupied molecular orbital (HOMO) at each site. The it-localization energy of the two C-8 and C-9 nitration transition state cr-complexes was better able to predict the observed ratio of products, which favors nitration at C-9 by 3 1 <2003M1629, 2004HAC263>. 

Application of the FMO theory allows the reactivity and regioselectivity of a particular diene/dienophile pair in a cycloaddition reaction to be reliably predicted. Cycloadditions involving electron-rich dienes and electron-deficient dienophiles are called normal electron demand cycloadditions. In this case the primary interactions in the transition structure are between the highest occupied molecular orbital (HOMO) of the diene and the lowest unoccupied molecular orbital (LUMO) of the dienophile. Reactions between electron-poor dienes and electron-rich dienophiles are called inverse electron demand cycloadditions, and the major interactions are between the LUMO of the diene and the HOMO of the dienophile. The regioselectivity can often be rationalized or predicted by matching the larger FMO coefficients in the corresponding FMO s of both reaction components. 

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