The Importance of the Ene Reaction for the C²−C⁶ Cyclization of Enyne−Allenes

Abstract

The present study establishes the ene reaction as a competing reaction mechanism to the diradical mechanism for the thermal C(2)-C(6) cyclization of enyne-allenes which possess bulky substituents at the alkyne terminus. Both reaction routes are found to possess nearly equal free energies of activation. As shown by our computations, primary H/D isotope effects could be used for a definite decision about the mechanism. Concerning the regioselectivity of the cyclization reactions of enyne-allenes our study resolves a long-standing deviation between theoretical results and experimental findings.

Elucidation of Nonstatistical Dynamic Effects in the Cyclization of Enyne Allenes by Means of Kinetic Isotope Effects

“…They predicted a stepwise process with the radicalstabilizing group R 1 = Ph and a concerted process with R 1 = tBu. [11] A recent study of the intermolecular KIE on the thermal ene process of enyne allene E4 with R 1 = triisopropylsilyl (TIPS), however, suggested a stepwise diradical process. [10] Lipton and Singleton analyzed the reaction for E1 by combining insight from a single intermolecular KIE value, theoretical calculations, and dynamic trajectories.…”

6 Reaction mechanisms : Part (ii) Pericyclic reactions

“…69 Instead of cyclization to a diradical intermediate, the authors propose that the product can be formed by an ene reaction. The alkyne acts as the enophile, and abstracts a hydrogen from a saturated substituent on the allene terminus.…”

New Insights into Cyclobutenone Rearrangements: A Total Synthesis of the Natural ROS‐Generating Anti‐Cancer Agent Cribrostatin 6

“…To test this hypothesis, the course of the reaction was modelled by DFT calculations at the UB3LYP/6-311GA C H T U N G T R E N N U N G (d,p) level with the Gaussian 09 program. [14,15] The estimated E + ZPVE values ( Figure 2, in green) were interesting in that they showed little difference between the activation barrier for electrocyclic ring opening (21.6 kcal mol À1 ) and ring closing (21.9 kcal mol…”

“…[15][16][17][18] Figure 3. Hammett plot for the arylcyclobutenone rearrangement 1!2 + 3 with the s I parameter set (&) and with a steric correction (s I À6 % E s , ).…”