Simple prediction of cycloaddition orientation

Approach to regiochemistry using local softness in 1,3-dipolar cycloadditions

“…We are not aware of whether any experimental evidence exists supporting this view. However, the hypothesis formulated by Anh and coworkers, 28 indicating that ''it is likely that the first bond would link the softest centers, i.e. the atoms giving the greatest overlap stabilization'' is in line with our assumption.…”

HSAB principle: Applications of its global and local forms in organic chemistry

“…This HSAB study performed at the local-local level provides an answer to Anh's long-pending hypothesis stating that "it is likely that the first bound would link the softest centers [22]. "…”

“…The predominance of orthoregioisomers in the cycloaddition of 1-substituted dienes 5 and asymmetrical dienophiles 6 (Scheme 2) cannot be explained by electronic effects, as replacement of an electron-donating substituent by an electronattracting one does not alter the regioselectivity as discussed by Eisenstein and co-workers [22].…”

Conceptual, Qualitative, and Quantitative Theories of 1,3‐Dipolar and Diels–Alder Cycloadditions Used in Synthesis

“…[26] Reactions of 1-substituted dienes with unsymmetrical dienophiles are of interest because replacement of an electron-withdrawing group with a donating group does not influence the regioselectivity. [27] Using the HF/3-21G method, they matched the local softness values for the ortho and meta regioisomers, and found that the vast majority of the 48 reactions had a smaller difference in softness for the ortho regioisomer than the meta one. This is in agreement with experimental results that give the ortho form as the major regioisomer.…”