A density functional study of the relative stability of intermediates in a McMurry coupling reaction

Abstract

The intramolecular McMurry reaction is a relatively common method for assembling carbocycles in organic synthesis. Most typically, this reaction involves a reductive coupling mediated by Ti(II). However, there are few examples of intramolecular McMurry reactions in the presence of Lewis basic heteroatoms. In this work, we investigate the titanium-mediated McMurry coupling leading to a pyrrolidine methoxy keto ester. Specifically, we compare the relative energies of all possible reaction intermediates at the B3LYP/6-31G level of theory. The most stable intermediate is found to be the one resulting from deoxygenation of the α-methoxy ketone. The McMurry product is not predicted to form.

Keywords:

• McMurry coupling
• Pyrrolidine keto ester
• Density functional
• Titanium

Notes

† A note about nomenclature: we label intermediates based on the ligand atoms bonding in the initial, pre-optimization structure. Intermediates are labeled [X,Y] to indicate that the titanium centers are bonded to atoms X and Y on the keto-ester.