Unveiling the Substituent Effects in the Stereochemistry of [3+2] Cycloaddition Reactions of Aryl‐ and Alkyldiazomethylphosphonates with Norbornadiene within a MEDT Perspective

Abstract

The [3 + 2] cycloaddition (32CA) reactions of norbornadiene with aryl and alkyl substituted diazomethylphosphonates (SDAPs) have been studied within the molecular electron density theory (MEDT). Electron localization function (ELF) shows the presence of a pseudoradical C3 center at the alkyl SDAPs, classifying them as pseudo(mono)radical species, while the aryl SDAP is classified as a zwitterionic one, owing to the delocalization of the C3 electron density on the C3-P bond. These 32CA reactions present high activation enthalpies in dichloromethane, between 17.3 and 21.6 kcal mol À 1 , being strongly exothermic by more than 33.8 kcal mol À 1 . While these 32CA reactions present a total syn facial selectivity, the endo/ exo stereoselectivity depends on the steric hindrance caused by the bulk substituents present in these SDAPs along the approach to norbornadiene. Interestingly the phenyl group provokes a lesser hindrance than that of the small methyl group, justifying the 95 % of exo stereoselectivity experimentally observed. ELF and the AIM (Atoms-in-Molecules) analyses account for the bonding changes along these 32CA reactions. The energy cost for the rupture of the norbornadiene CÀ C and that of the SDAPs NÀ N double bonds are the major contributors to the activation energies of these non-polar 32CA reactions.

Unveiling the intramolecular [3 + 2] cycloaddition reactions ofC,N-disubstituted nitrones from the molecular electron density theory perspective

“…Additionally, the stepwise 32CA mechanism 27 is also well known in nitrone chemistry. MEDT has been successfully applied to study various aspects of 32CA reactions in the last six years, such as strain promotion, 28,29 regioselectivity, 30 influence of catalysts, 31,32 chemoselectivity, 33,34 stereoselectivity, 33,35 substituent effects, 36,37 etc. In 2018, Domingo et al 38 reported the MEDT study to analyze the fused regioselectivity in the IM32CA reactions of cyclic nitrones.…”

Unveiling the Mg(ii) promoted [3+2] cycloaddition reaction of mesitonitrile oxide to Baylis–Hilman adduct from the molecular electron density theory perspective

“…15 Thus, while pdr-type 32CA reactions take place very easily, zw-type 32CA reactions demand suitable nucleophilic/electrophilic activations. Regio, 16,17 stereo, 17–19 and chemoselectivity, 20,21 catalysis, 22,23 strain promotion, 24,25 substituent effects, 26,27 unexpected reactivity 28 and other aspects of chemical reactions have been successfully analyzed using the MEDT framework.…”

Unveiling substituent effects in [3+2] cycloaddition reactions of benzonitrile N-oxide and benzylideneanilines from the molecular electron density theory perspective

“…In 2016, Domingo proposed the molecular electron density theory [8] (MEDT) to establish the role of electron density changes on molecular reactivity. Since last seven years, the MEDT perspective has been successfully applied to analyse the experimentally observed region [9,10], stereo- [9][10][11][12] and chemoselectivity [13,14], reactivity [15][16][17], substituent effects [18,19], catalysis [20,21], strain promotion [22,23] and several other aspects of 32CA reactions [24,25]. Recently, we have reported the MEDT analysis of the chemo and regioselectivity observed in the 32CA reaction of 4-chlorobenzonitrile N-oxide and β-aminocinnamonitrile for construction of 1,2,4oxadiazoles [26].…”