Theoretical Study To Explain How Chirality Is Stored and Evolves throughout the Radical Cascade Rearrangement of Enyne-allenes

• Published in: Journal of organic chemistry 2014-10, Vol.79 (19), p.9086-9093
• Main Authors: Gaudel-Siri, Anouk, Campolo, Damien, Mondal, Shovan, Nechab, Malek, Siri, Didier, Bertrand, Michèle P
• Format: Article
• Language: English
• Subjects: Alkadienes - chemistry; Alkynes - chemistry; Chemical Sciences; Cyclization; Models, Theoretical; Molecular Structure; or physical chemistry; Stereoisomerism; Theoretical and
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo501450k

This article reports a theoretical study to explain how the intrinsic property of chirality is retained throughout the radical cascade rearrangement of an enantiopure chiral enyne-allene (bearing one stereogenic center) selected as a model for this family of reactions. Calculations at the MRPT2/6-31G­(d)//CASSCF­(10,10)/6-31G­(d) level of theory were used to determine the entire reaction pathway which includes singlet state diradicals and closed-shell species. The cascade process involves three elementary steps, i.e., by chronological order: Myers–Saito cycloaromatization (M-S), intramolecular hydrogen atom transfer (HAT), and recombination of the resulting biradical. The enantiospecificity of the reaction results from a double transmission of the stereochemical information, from the original center to an axis and eventually from this axis to the final center. The first two steps lead to a transient diradical intermediate which retains the chirality via the conversion of the original static chirogenic element into a dynamic one, i.e., a center into an axis. The only available routes to the final closed-shell tetracyclic product imply rotations around two σ bonds (σ­(C–C) and σ­(C–N), bonds β and α respectively). The theoretical calculations confirmed that the formation of the enantiomerically pure product proceeds via the nonracemizing rotation around the σ­(C–C) pivot. They ruled out any rotation around the second σ­(C–N) pivot. The high level of configurational memory in this rearrangement relies on the steric impediment to the rotation around the C–N bond in the chiral native conformation of the diradical intermediate produced from tandem M-S/1,5-HAT.