Leaving groups selective activation

In comparing the reactivity at different positions in a heterocycle, a poly-substituted derivative is sometimes used with the idea that selective reaction of the same leaving group at different positions in a single molecule gives the most clear-cut answer. However, in a polychloroazine, the mutual activation of the chlorines by one another is not identical (unless the molecule is symmetrical, in which case the... 

Based on the three-dimensional structure of CHS, we proposed that the initiation/elongation/cyclization cavity serves as a structural template that selectively stabilizes a particular folded conformation of the linear tetraketide, allowing the Claisen condensation to proceed from C6 to Cl of the reaction intermediate.14 In contrast, CTAL formation can occur either in solution or alternatively while sequestered in the enzyme active site. In either case, enolization of the C5 ketone followed by nucleophilic attack on the Cl ketone with either a hydroxyl group (in solution) or the cysteine thiolate (enzyme bound) as the leaving group results in CTAL. Similar lactones are commonly formed as by-products of in vitro reactions in other PKS systems.36 38... 

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