Frontier Molecular Orbitals and Pericyclic Reactions Vincent N. G. Lindsay Cyril Nicolas Problem Set February, 2nd, 2010

if [3,5] sigmatropic rearrangement [3,5] supra-supra not allowed Problem 1 In a “recent” paper (e.g., Org. Lett. 2003, 5, 2619) Uemura and co-workers have reported the preparation of furan-containing sulfide derivatives. In the study, they observed that product 1 was thermally labile, and gradually isomerized to give another structural form (2) at ambient temperature. The mechanism proposed, was a [3,5] sigmatropic rearrangement. Provide an FMO analysis that illustrates why, this is not a plausible mechanism. Also, provide a mechanism for this rearrangement that would be more consistent with the orbital symmetry rules. Migration supra supra if [3,5] sigmatropic rearrangement [3,5] supra-supra not allowed

Problem 1 Migration supra supra (D) Migration supra supra (D) [3,3] supra supra allowed

Problem 2 Berson and co-workers have studied the following thermal isomerization (J. Am. Chem. Soc. 1966, 88, 2494). Propose a rationale for these results using three-dimensional drawings and FMO analysis.

Problem 2 Berson and co-workers have studied the following thermal isomerization (J. Am. Chem. Soc. 1966, 88, 2494). Propose a rationale for these results using three-dimensional drawings and FMO analysis.

Problem 2 Berson and co-workers have studied the following thermal isomerization (J. Am. Chem. Soc. 1966, 88, 2494). Propose a rationale for these results using three-dimensional drawings and FMO analysis.

Problem 2 Berson and co-workers have studied the following thermal isomerization (J. Am. Chem. Soc. 1966, 88, 2494). Propose a rationale for these results using three-dimensional drawings and FMO analysis.

Problem 3 Upon irradiation and subsequent work-up, 3 undergoes two sequential reactions to give 4 as the only product (J. Chem. Soc. Perkin Trans. 1973, 505). Provide a mechanistic rationale for the transformation and predict the final stereochemistry of the product. Also, explain why the thermal reaction would probably afford a totally different result. For this, you should take into consideration frontier molecular orbital diagrams.

Problem 3 Geometry of the intermediate does not permit antarafacial light induced 1,5 shift

Problem 4 The acetylene alkoxide (ynolate) 5 reacts with para-substituted acetophenones (6) to give, respectively (E) and (Z) unsaturated acids 7 and 8. Interestingly, along the experiment, it was determined that the (E):(Z) ratio strongly depends on the substituent on the aromatic ring (vide infra). Using Kékulé-Couper drawings and FMO theory provide a mechanism that could account for both, the overall transformation and stereoelectronic issues.

Problem 4 When sterics are dominant R = H, NMe2 phenyl group out path a phenyl group in path b 4 electrons electrocyclization = conrotatory under thermal conditions When stereoelectronics are dominant R = NO2

Problem 5 Hsung et al. have reported the diastereoselective reaction shown below (Org. Lett. 2000, 2, 1161). While there is a mechanistic ambiguity associated with this process, the authors have suggested that the stereochemical-determinig step would probably proceed in a concerted pericyclic manner. Using FMO analysis and 3D drawings propose a concise mechanism which is consistent with the sense of asymmetric induction observed in the reaction.

2 possible disrotatory ring-closures Problem 5 2 possible disrotatory ring-closures Steric interactions