Understanding chemical reactivity using the activation strain model

Abstract

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Ambident Nucleophilic Substitution: Understanding Non‐HSAB Behavior through Activation Strain and Conceptual DFT Analyses

“…The Pauli repulsion, DE Pauli (z), accounts for the destabiliz-ing interaction between occupied orbitals (more precisely,b etween same-spine lectrons) and is responsible for steric repulsion. [34] The orbitali nteraction energy, DE oi (z), accountsf or donor-acceptor interactions of occupied orbitals on one fragment with unoccupied orbitals on the other (such as the HOMO-LUMO interaction) and polarization,t hat is, the mixing of empty and occupied orbitals on one fragment due to the presence of the other.Adetailed step-by-step protocol on how to perform and interpret the activation strain and energy decomposition analysiscan be found in reference [35].…”

Optimized Synthesis of 7-Aza-Indazoles by Diels–Alder Cascade and Associated Process Safety

“…1-Benzyl-3-cyclohexyl-5-iodo-4-phenyl-1H-pyrazolo [3,4-b]pyridine 17 was obtained as a white solid (1.03 g, 84 %). Upon scaling-up of this reaction on 3.77 g of 16, 1-benzyl-3-cyclohexyl-5-iodo-4-phenyl-1H-pyrazolo [3,4- 2929, 2851, 1551, 1483, 1442, 1347, 1271, 1189, 1175 (Z)-2-(2-(1-Cyclohexyl-3-phenylprop-2-yn-1-ylidene)hydrazinyl)-5-iodopyrimidine (18). To a Schlenk tube containing dry 3Å molecular sieves (100 mg) were successively added 2-hydrazinyl-5-iodo-pyrimidine 10 (112.5 mg, 0.48 mmol), THF (2.4 mL, 0.2 M), 1-cyclohexyl-3-phenylprop-2-yn-1-one 15 (131.55 mg, 0.62 mmol) and trifluoroacetic acid (5 μL, 0.067 mmol, 15 mol%) under nitrogen.…”

“…[1][2][3][4][5] A limitation of this conceptually interesting synthesis of pyridines are the high temperature (up to 280 °C under classical conditions 6 ) and very long reaction times that are required [7][8][9] to overcome the intrinsic lack of reactivity of these aza-dienes. [10][11][12][13][14][15][16][17][18][19] On the other hand, we recently reported that pyrimidines substituted in the 2-position by an (alkynyl)hydrazone could be exceptionally activated towards intramolecular [4ps+2ps] cycloadditions by a simple activation (Scheme 1, A). 20 In a practical one-pot procedure starting from 2-hydrazinopyrimidine 2, it was shown that condensation with ynone 3 in the presence of catalytic amount of trifluoroacetic acid was rapid at 60 °C in THF, leading to hydrazone 4.…”

Stereoretention in styrene heterodimerisation promoted by one-electron oxidants

“…To further understand the steric and electronic factors inuencing the head-to-head vs. head-to-tail regioselectivity, we applied the distortion-interaction 91,92 /activation strain (DI-AS) model [92][93][94][95][96] to the TSs for the formation of rst C-C bond for the present reaction (Fig. 3).…”

“…We further applied the method of energy decomposition analysis (with the ALMO-EDA method), [97][98][99] as applied in other similar systems, 94,96,[100][101][102] to break down the contributions to the interaction energy between the reacting fragments into the repulsive exchange energy due to Pauli's principle, E Pauli , the (semi-)classical electrostatic interaction energy between the charge densities of the fragments, E elec , the orbital interaction energies between the fragments as the TS occurs, E orb , and the dispersion energy between the fragments E disp . Comparing the EDA between the major, anti-adduct via ts1 to other TSs (Fig.…”