Metal‐free Kinugasa reaction catalyzed by external electric field

Abstract

AbstractOriented external electric field (OEEF) is in recent interest for its ability to promote reactivity and selectivity in chemical transformations. This article reports facile metal‐free [3 + 2] cycloaddition for the Kinugasa reaction in the presence of OEEF. The free energy of activation is reduced by 4.9 kcal/mol due to a parallel electric field in the orthogonal direction to the reaction axis, Fy = 5.0 V Å−1. As a proof‐of‐principle of this model, a multidrug‐resistant (MDR) antibiotic, carbapenem could be envisioned from the [3 + 2] cycloaddition of a cyclic nitrone and an acetonide substituted acetylene. This reaction shows an interesting ambiaxial electric field‐induced catalysis with a reduced reaction barrier for anti‐parallel fields, −Fx (reaction axis) and −Fz and parallel field along +Fy. This is due to the out‐of‐plane bending of the acetonide unit containing two highly electronegative oxygen atoms. As a result, off‐axial tensorial responses to the electric‐fields on the barriers are observed. Such ambiaxial OEEF driven catalysis is interesting because it expands the utility of electric fields for large enzymes. Disorder and dynamical effects of side chains are envisioned to cause non‐null responses to applied field for parallel or anti‐parallel directions along axes.