Evidence for Dearomatizing Spirocyclization and Dynamic Effects in the Nitrogen Deletion of Tetrahydroisoquinolines

A detailed mechanistic analysis of the nitrogen deletion of 1-aryl-tetrahydroisoquinolines is presented, suggesting that the anticipated diradical mechanism undergoes dynamically controlled partitioning to both the normal 1,5-coupling product and an unexpected spirocyclic dearomatized intermediate, which converges to the expected indane by an unusually facile 1,3-sigmatropic rearrangement. This mechanism is not reproduced by static DFT but is supported by quasi-classical molecular dynamics calculations and unifies several unusual observations in this system, including partial chirality transfer, non-statistical isotopic scrambling at the ethylene bridge, and the isolation of spirocyclic dearomatized species in a related heterocyclic series. This latter family of compounds exhibit sterically controlled E/Z selectivity ranging from >20:1 to <1:20, prompting the consideration of an analogous cis isomer in the parent transformation. However, despite the observation that an 8-methyl substituent dramatically increases enantiospecificity, calculations indicate that this effect is best explained by dynamic torsional locking of the intermediate diradical.