We report the dynamical trajectory study of the transannular [6+4] and ambimodal cycloaddition proposed in the biosynthesis of heronamide natural products. The originally proposed bifurcation of the potential energy surface is found to strongly favor the formation of the [6+4] product, both in the gas phase and in an explicit water environment, as evidenced by our trajectory simulations. The detailed information on how the bonds are formed and how water influences the bonding dynamics was analyzed at the femtosecond time scale.