Mechanisms and Origins of Periselectivity of the Ambimodal 6 + 4 Cycloadditions of Tropone to Dimethylfulvene

The mechanisms and selectivities of the cycloadditions of tropone to dimethylfulvene have been investigated with M06-2X and B3LYP-D3 density functional theory (DFT) calculations and quasi-classical direct molecular dynamics simulations. The originally proposed reaction mechanism (Houk) involves a highly peri-, regio-, and stereoselective 6 F + 4 T cycloaddition of tropone 4π to dimethylfulvene 6π, followed by a 1,5 hydrogen shift, and, finally, a second 6 + 4 cycloaddition of tropone 6π to the cyclopentadiene moiety 4π. Paddon-Row and Warrener proposed an alternative mechanism: the initial cycloaddition involves a different 6 T + 4 F cycloaddition in which fulvene acts as the 4π component, and a subsequent Cope rearrangement produces the formal 6 F + 4 T adduct. Computations now demonstrate that the initial cycloaddition proceeds via an ambimodal transition state that can lead to both of the proposed 6 + 4 adducts. These adducts can interconvert through a 3,3 sigmatropic shift (Cope rearrangement). Molecular dynamics simulations reveal the initial distribution of products and provide insights into the time-resolved mechanism of this ambimodal cycloaddition. Competing 4 + 2 cycloadditions and various sigmatropic shifts are also explored.