Regioselectivity of 1,3-dipolar cycloadditions between aryl azides and an electron-deficient alkyne through DFT reactivity descriptors

Abstract

Conceptual density functional theory, including chemical hardness, electronic chemical potential, global and local electrophilicity index and Fukui functions, is used to predict reactivity and regioselectivity of 1,3-dipolar cycloadditions (13DCs) between five aryl azides (1–5) and an electron-deficient alkyne at the B3LYP/6-31G(d,p) level. Two reaction paths (a) and (b) are considered which result in the corresponding regioisomeric 1,2,3-triazoles P(1-5)a and P(1-5)b, respectively. All the 13DCs proceed via rather asynchronous TSs and the path (b) is clearly more synchronous than the path (a). All the reactions are high exoergic [∆Go = −45.1 to −51.4 kcal/mol for path (a) and −47.7 to −55.9 kcal/mol for path (b)] with the moderate and nearly similar activation barriers (E a = 15.4–16.7 kcal/mol) referring a relatively low regioselectivity. All reactivity descriptors but one clearly suggest that path (a) is somewhat preferred over path (b). FMO interactions occur between HOMO13DP and LUMODPh due to the corresponding lower energy gap. All the reactions considered in this work classified as polar 13DCs with NED character. Our theoretical results are in good agreement with those reported experimentally.