Quantum Chemical Characterization of Factors Affecting the Neutral and Radical-Cation Newman-Kwart Reactions

Abstract

Details of the electronic and geometric structures of stationary points along the reaction coordinate of the Newman Kwart rearrangement, which transforms an O-arylthiocarbamate to an S-arylcarbamothioate, are examined using quantum chemical methods for a large number of compounds considering both the thermal reactions of uncharged substrates as well as the corresponding reactions of radical cation substrates generated under photoredox conditions. The uncharged mechanism, which has intrinsically high 298 K free energies of activation (in excess of 30 kcal.mol–1), has the character of nucleophilic aromatic substitution and is thus accelerated by electron-withdrawing substituents on the aromatic ring. The radical cationic mechanism, by contrast, has 298 K free energies of activation that are typically below 20 kcal.mol–1, and is accelerated by electron donating substituents on the aromatic ring, which stabilize the hole character that is transferred to this fragment from the thiocarbamate fragment as the reaction proceeds. Opportunities to further accelerate the radical cation reaction are revealed by computational assessment of alternative amino groups for the thiocarbamate functionality.

Mechanistic Investigations into the Cation Radical Newman–Kwart Rearrangement

“…17 It is of note that the conclusions drawn from our experiments are consistent with the results predicted from two computational studies of the cation-radical NKR that were published during the preparation of this manuscript. 17,39 Heterolytic scission of the O-aryl bond in the activated complex would give rise to intermediate 2 +• , which has cation radical character localized on the arene. Subsequent reduction furnishes the desired S-aryl product.…”

Unraveling the role of the electron-pair density symmetry in reaction mechanism patterns: the Newman–Kwart rearrangement

“…The works of Kwart and Evans, 1 on the one hand, and Newman and Karnes, 2 on the other, led to the identification of the molecular mechanism we now call the Newman-Kwart rearrangement (NKR). The NKR is a thermally induced process encompassing the migration of O-aryl thiocarbamates to the corresponding S-aryl compounds, [3][4][5][6][7][8][9] as depicted in Scheme 1.…”

“…High temperatures are required to overcome the energy activation barrier ranging from 35 to 43 kcal mol À1 ; 5,9,10 however, such temperature values lead to some difficulties that decrease the reaction's organic synthesis potential. 5,9,10 Despite these drawbacks, the NKR has been extensively investigated from both experimental and theoretical approaches, providing a broad range of applications in critical areas, including supramolecular chemistry, 11,12 pharmaceutical intermediates, 13,14 dyes, 15 molecular switches, 16 and chiral ligand synthesis, 17,18 among others.…”

“…From a theoretical/computational point of view, several modern interests based on the applications of density functional theory (DFT) 19 are simply oriented to probe whether the aromatic migration O Ar -S Ar (see Scheme 1) proceeds via a four-membered transition state, 3 or to elucidate the activation barriers. 6,9 Curiously, much less attention has been devoted to studying the remarkable features of the electron density flow driving the transformation. A deeper understanding of the NKR mechanism requires detailed knowledge concerning electron reorganization to reveal the underlying essential bonding sequences.…”