Remarkable temperature effect on intramolecular [3 + 2] cyclization

Gromov, Alexey; Enev, Valentin; Mulzer, Johann.   

Tetrahedron Letters  (2009),  50(37),  5283-5284.

A preference of intramolecular cyclizations over oligomerization can often be achieved by conducting the reaction at higher temperatures. This effect which has obviously been underestimated so far may be useful in synthetic organic chemistry. Herein, we report a novel example supporting this observation—an intramolecular nitrile oxide 1,3-dipolar cycloaddition. The yield of the desired product rose from 53% at 0 °C to 79% at 80 °C. A plausible kinetic background of this phenomenon is proposed in terms of activation enthalpy.