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 [4 pi] to dimethylfulvene [6 pi], followed by a [1,5] hydrogen shift, and, finally, a second [6 + 4] cycloaddition of tropone [6 pi] to the cyclopentadiene moiety [4 pi]. 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 4 pi 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.