Violations. How Nature Circumvents the Woodward–Hoffmann Rules and Promotes the Forbidden Conrotatory 4n + 2 Electron Electrocyclization of Prinzbach’s Vinylogous Sesquifulvalene

Abstract

Woodward and Hoffmann, in their treatise on orbital symmetry in 1969, stated "Violations. There are none!" Prinzbach reported in 1978 that the electrocyclization of vinylogous sesquifulvalene occurs exclusively through the Woodward−Hoffmann orbital-symmetry-forbidden 14π-electron conrotatory pathway, despite the availability of a variety of orbital-symmetry-allowed processes. Prinzbach later demonstrated that an 18π-electron homologue exhibits the same forbidden behavior. And yet, the analogous vinylogous pentafulvalene and heptafulvalene both follow the orbital symmetry rules, each proceeding through its allowed conrotatory 12π and 16π process, respectively. We report the investigation of these reactions with ωB97X-D DFT. The physical origins of the flagrant Prinzbach violations of the Woodward−Hoffmann orbital symmetry selection rules have now been elucidated by these calculations in conjunction with extensive analyses and comparisons to electrocyclizations that obey the Woodward−Hoffmann rules. This remarkable reversal of the Rules (the 14π-electron-forbidden process is found to be 11 kcal/mol more energetically facile than the allowed process) occurs due to the high degree of polarization of this hydrocarbon, such that conrotatory electrocyclization of vinylogous sesquifulvalene behaves like a cyclopentadienide combining with a tropylium. These results are compared to other forbidden pericyclic processes driven by steric constraints and strain release or by diradical character of the reactants that facilitates the formation of diradical transition states for symmetry-forbidden reactions. We predict how strong donor−acceptor substitution can modify nodal properties to level the difference between allowed and forbidden electrocyclic reaction barriers, and we provide computational predictions of two such cases.

Prediction of High-Yielding Single-Step or Cascade Pericyclic Reactions for the Synthesis of Complex Synthetic Targets

“…The thermally forbidden, but experimentally accessible, TS between 62 and 65 was calculated to be Δ G ‡ = 22.6 kcal/mol, which is very similar to the value calculated by Houk (Δ G ‡ = 22.3 kcal/mol). In addition, the formation of the more stable indene 64 was also observed after two suprafacial [1,5]-hydrogen shifts, which is in good agreement with the experimental result by Prinzbach . It should also be noted here that the thermally forbidden, but experimentally accessible pathway can be searched automatically, which greatly enhances the practical utility of this AFIR-based retrosynthetic analysis.…”

“…In addition, the formation of the more stable indene 64 was also observed after two suprafacial [1,5]hydrogen shifts, which is in good agreement with the experimental result by Prinzbach. 16 It should also be noted here that the thermally forbidden, but experimentally accessible pathway can be searched automatically, which greatly enhances the practical utility of this AFIR-based retrosynthetic analysis. Reported pericyclic reactions are usually conducted under neat conditions 23−26,28 or using a nonpolar solvent (toluene or benzene) 14d,27,30,32 at elevated temperatures, which is well suited to our gas-phase calculations.…”

“…Very recently, Houk and coworkers reported an elegant mechanistic study of thermally forbidden 14π electrocyclic reactions for Prinzbach's vinylogous sesquifulvalene 62, 32 wherein the thermically allowed disrotatory 14π electrocyclic reaction that affords cis-product 61 is disfavored compared to the thermally forbidden conrotatory pathway that affords trans-product 65 because of the electronic and steric constraints in the TS (violations of the Woodward−Hoffmann rules). 16 Encouraged by Houk's report, we first subjected the disfavored cis-product 61 to the QCaRA (Figure 8a; 26 atoms), which successfully afforded reactant 62 after the calculation of 710 EQs and 1468 PTs. In addition, the formation of the more stable indene 64 was observed after two suprafacial [1,5]-hydrogen shifts.…”

“…Even with the approximate TS, however, the activation energy (ΔG ‡ = 32.9 kcal/mol) is very similar to the value calculated by Houk (ΔG ‡ = 33.5 kcal/mol). 16 Next, the favored trans-product 65 was calculated, which generated reactant 62 and indene 64 after 719 EQs and 1416 PTs (Figure 8b; 26 atoms). The N-yield of trans-product 65 indicated a different tendency from that of the cis-product: At 300 K, 65 would be obtained as the product from 62, while at 400 and 500 K, the product would be altered from 62 to 64.…”

Understanding chemistry: from “heuristic (soft) explanations and reasoning by analogy” to “quantum chemistry”

“…121 [2 + 2] cycloadditions are fine thermallyif the appropriate orbital symmetry-required geometries can be achieved and a high energy barrier can be overcome, or if the substituents cause significant asymmetry and the reaction proceeds by a non-Woodward-Hoffmann pathway. [122][123][124] (bottom) Examples of valence isomerizations in vitamin D chemistry. [125][126][127] Importantly, these are examples of alternating stereospecific reactions, alternation in the number of electrons involved and whether the reactions are thermal or photochemical.…”