Unveiling the high reactivity of cyclohexynes in [3 + 2] cycloaddition reactions through the molecular electron density theory

Luis R. Domingo, Mar Ríos-Gutiérrez, Patricia Pérez

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

[3 + 2] cycloaddition (32CA) reactions of cyclohexyne, a cyclic strained acetylene, with methyl azide and methoxycarbonyl diazomethane have been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G(d) computational level. These 32CA reactions, which take place through a one-step mechanism involving highly asynchronous transition state structures, proceed with relatively low activation enthalpies of 6.0 and 4.3 kcal mol-1, respectively, both reactions being strongly exothermic. The reactions are initiated by the creation of a pseudoradical center at one of the two acetylenic carbons of cyclohexyne with a very low energy cost, 1.0 kcal mol-1, which promotes the easy formation of the first C-N(C) single bond in the adjacent acetylenic carbon. This scenario is completely different from that of the 32CA reaction involving non-strained but-2-yne; thus, strain in cyclohexyne triggers a high reactivity as a consequence of its unusual electronic structure at the ground state. Finally, the experimental regioselectivity of the 32CA reactions involving 3-alkoxy-cyclohexyne derivatives is correctly explained within MEDT.

Original languageEnglish
Pages (from-to)498-508
Number of pages11
JournalOrganic and Biomolecular Chemistry
Volume17
Issue number3
DOIs
Publication statusPublished - 1 Jan 2019

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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