Application to (3 + 2) azide–alkyne cycloaddition reactions.
Delocalization, not strain release, explains the enhanced reactivity
of dibenzocyclooctyne over cyclooctyne in (3 + 2) cycloadditions with
methyl azide. (a) BEP plot (predicted vs calculated ΔH‡, kcal mol–1) for
the addition of methyl azide to the red bonds of the alkynes in the
test set. The blue dashed line denotes perfect correlation. (b) Prediction
of ΔH‡ from ΔHr and χNBO (eq 3). (c) Breakdown of strain release
and delocalization (χNBO) contributions to ΔΔH‡ (kcal mol–1) for
the addition of methyl azide to the test set relative to cyclooctyne
(A4), following the protocol in Figure 3d. Asterisks indicate the cases where delocalization
dominates over strain release, and superscripts a and s refer to anti and syn TSs,
respectively.