Strain-Enabled Ene-Yne Metathesis with Atom Economy: Access to Strained and Highly Substituted 1,3-Dienes

In this work, angle strain in a geminally substituted alkene reactant enabled ene-yne metathesis reactions of a wide alkyne and alkene substrate scope. Methylene cyclobutanes and methylene azetidines served as the angle-strained alkene reactants, and both terminal and internal alkynes were found to react. Angle strain results from geometric distortion by the four-membered ring away from the idealized trigonal planar geometry of the sp² hybridized carbon atom. Highly atom economical ene-yne metathesis reactions were developed using 1:1 reactant stoichiometry and 1 mol % of a Grubbs-type catalyst in most cases. Complete atom economy describes the rare case when all of the atoms of reactants go into the products without any waste, which is an important metric for efficiency and sustainability in organic reactions. In these catalytic reactions, angle strain in the alkene reactant is still present in the 1,3-diene products; therefore, angle strain is not lost in the ene-yne metathesis. The presence of angle strain in 1,3-diene facilitates secondary metathesis and cycloaddition reactions of the 1,3-diene products, showing an activating effect on these subsequent reactions. To better understand how strain facilitates the catalytic reaction, DFT calculations were performed. A cyclic, strained alkene reactant was compared with an acyclic, unstrained reactant to pinpoint the key energetic differences. These studies showed that angle strain enabled an alkene-first initiation step and lowered the activation energy of the alkyne insertion step in the ene-yne metathesis catalytic cycle. A further study in a model system showed that angle strain raised the energy of the reactants and had a less destabilizing effect on key reactive intermediates as well as the cycloaddition and cycloreversion transition states.