Computational assessments of diastereoselective [4+2] cycloaddition and 1,3-borotopic shift of a dearomatized tertiary boronic ester intermediate: reactivities explained through transition-state distortion energies

Aqeel A Hussein; Faisal A Almalki; Alaa M Alqahtani; Sergey Shityakov

doi:10.1039/c9ra03820e

Computational assessments of diastereoselective [4+2] cycloaddition and 1,3-borotopic shift of a dearomatized tertiary boronic ester intermediate: reactivities explained through transition-state distortion energies

RSC Adv. 2019 Jul 26;9(40):23148-23155. doi: 10.1039/c9ra03820e. eCollection 2019 Jul 23.

Authors

Aqeel A Hussein^{1

2}, Faisal A Almalki³, Alaa M Alqahtani³, Sergey Shityakov⁴

Affiliations

¹ Faculty of Dentistry, University of Al-Ameed Karbala P.O. No: 198 Iraq.
² Department of Chemistry, University of Southampton Southampton Hampshire SO17 1BJ UK aahh1f19@soton.ac.uk.
³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University Makkah 21955 Saudi Arabia.
⁴ Department of Anesthesia and Critical Care, University of Würzburg 97080 Würzburg Germany.

Abstract

Interception of a dearomatized tertiary boronic ester, formed through a kinetically and thermodynamically favorable 1,2-metalate rearrangement/anti-S_N2' elimination of an activated ortho-lithiated benzyl amine, in a [4+2] cycloaddition or 1,3-borotopic shift has been investigated by density functional theory (DFT). Although superacitvated "naked" Li⁺ was found to greatly promote 1,3-borotopic shift, the diastereoselective [4+2] cycloaddition was favored. It was revealed that the factor that controls the diastereoselectivity was the steric bulk provided by the diene, which is in agreement with experimental diastereoselectivity. A comparison of unreactive dienophiles such as maleic anhydride, diethyl maleate, and others with 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione (PTAD) was found to be in an excellent agreement with the experiments; where their lack of reactivity is attributed to the high deformation energies of the interacting components to achieve the transition state structure which was pronounced with the high energy of LUMO orbitals.