Lithium Choreography Determines Contrasting Stereochemical Outcomes of Aryl Migrations in Benzylic Carbamates, Ureas and Thiocarbamates

The intramolecular arylation reactions of lithiated derivatives of ureas, carbamates and thiocarbamates generally proceed stereospecifically, but the reaction is stereochemically retentive with ureas and thiocarbamates, whereas it is stereochemically invertive with carbamates. Using DFT calculations, we have studied the mechanism of the intramolecular attack of a thiocarbamate-stabilised carbanion on an N-aryl substituent and compared the details of the calculated reaction pathway with the corresponding reactions of carbamate- and urea-stabilised carbanions. The different stereochemical outcomes observed in the rearrangements of carbamates and thiocarbamates arise from the sulfur–carbon interaction in the thiocarbamate, which enhances the stabilisation of the anion. As a result, the solvated lithium cation takes different pathways across the potential energy surfaces that lead to stereochemically divergent outcomes. Additionally, we investigated the importance of the intramolecular nature of the aryl migration and compared the pathway for aryl migration within a urea with that of a hypothetical, experimentally unfeasible, intermolecular reaction. The results throw light on the reason why aryl migrations are successful even with much more electron-rich rings than would be tolerated in a typical intermolecular nucleophilic aromatic substitution.