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Regio‐ and Stereoselectivity in 1,3‐Dipolar Cycloadditions: Activation Strain Analyses for Reactions of Hydrazoic Acid with Substituted Alkenes
Author(s) -
Vilhena Felipe S.,
Bickelhaupt F. Matthias,
Carneiro José W. M.
Publication year - 2017
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201700577
Subject(s) - hydrazoic acid , regioselectivity , chemistry , cycloaddition , stereoselectivity , reactivity (psychology) , polar effect , sodium azide , 1,3 dipolar cycloaddition , density functional theory , homo/lumo , stereochemistry , strain (injury) , medicinal chemistry , computational chemistry , organic chemistry , molecule , catalysis , medicine , alternative medicine , pathology
We quantum chemically explore and analyze 1,3‐dipolar cycloadditions of hydrazoic acid and methyl azide with a number of substituted alkenes R‐HC=CH 2 (R = CH 3 , OH, OCH 3 , NH 2 , CN, and NO 2 ) by using dispersion‐corrected DFT at wB97X‐D/6‐311++G(d,p). Our purpose is to uncover the physical factors behind the computed trends in reactivity, regioselectivity (1,4 vs. 1,5 addition), and preferred stereochemistry ( endo vs. exo ). To this end, we use the activation strain model (ASM) and quantitative molecular orbital (MO) theory. One of our main findings is that introducing electron‐donating groups in the dipolarophile, R = CH 3 , OH, OCH 3 , or NH 2 , favors the 1,5‐cycloaddition. On the other hand, the presence of electron‐withdrawing groups, R = CN or NO 2 , leads to 1,4‐addition. Besides, we find a general preference for endo addition, a result that consolidates the endo rule. Trends in the regiochemistry are dictated by the inverse and regular HOMO–LUMO gap, respectively, between dipole and dipolarophile.