To calculate E for a molecule, 10 conformers of intermediate 2 are embedded using ETKDG as implemented in a slightly modified version of RDKit based on 2023.03.2, see subsection S1, and an RMSD pruning threshold of 0.25 Å is applied. The retained conformers are optimized at the GFN2-xTB level of theory. The lowest energy conformer is further optimized at the B3LYP-D3BJ/3-21 level and its single point energy is calculated as the B3LYP-D3BJ/def2-TZVP level using ORCA 5.0.4. The fragments R1-X (HC CH 2 ) and X (Br) are removed from the optimized structure to obtain a structure of intermediate 1 which undergoes optimization and single point calculation at the B3LYP-D3BJ/def2-TZVP//B3LYP-D3BJ/3-21 level of theory.