[1,5]-Sigmatropic Shifts Regulated by Built-in Frustration

Conceptually, many organic reactions involve a flow of electron density from electron-rich to electron-poor regions. When the direct flow of electron density is blocked, the innate "frustration" can provide a driving force for a reaction that removes the blockade. Herein, we show how this idea can be used for the design of molecular rearrangements promoted by remotely placed donor-acceptor pair of substituents. We evaluate effects of such "frustration" on the rates of competing [1,5]-hydrogen and [1,5]-halogen shifts in boron-substituted 1,3-pentadienes. As the sp³ hybridized carbon (C1) in these dienes interrupts the conjugation path between the donor to the acceptor, the system conceptually resembles a frustrated Lewis pair (FLP). Frustration is weakened when the formation of a new chemical bond in the TS opens communication between electron-rich and -poor regions and is removed completely when the resonance interaction between donor and acceptor develops fully in the rearranged product. Such relief of chemical frustration is directly translated into more favorable thermodynamic driving force and decreased intrinsic activation energies. Marcus theory separates thermodynamic contribution to the activation barriers and suggests that the electronic communication between electron rich and poor regions lowers the activation barrier via the formation of stabilizing 3-center contacts in the TS. Dramatic TS stabilization illustrates that the migrating groups function as an electronic relay between migration origin and terminus with properties fine-tuned by the boronyl acceptor. The combined effects of the C-X bond strength (X = migrating group), Lewis acidities of the acceptors, thermodynamic driving forces, and secondary orbital interactions control the observed barrier trends and selectivity of migration.