The Cycloaddition Reaction Between α-Bromo Vinylketenes and Imines: A Combined Experimental and Theoretical Study

The unusual behaviour of alpha-bromo vinylketenes in the cycloaddition reactions with imines is described. This class of vinylketenes behaves as dienophiles in [2+2] reactions, but also displays an unusual diene reactivity in [4+2] reactions. Interestingly, the reactivity of alpha-bromo vinylketenes can be modulated via a fine tuning of the substituents. For instance, a methyl group in the beta-position completely inhibits the [2+2] reaction and the [4+2] pathway is almost exclusively followed. A more hindered ketimine (instead of a simple imine) is enough to activate again the [2+2] mechanism. We have carried out a DFT theoretical investigation to rationalise these experimental observations. We have considered two pathways for the [2+2] reaction involving imine, that is, the endo and exo pathways. The former is favoured in the case of alpha-bromo vinylketenes, while the latter is preferred for non-substituted vinylketenes. Since the [4+2] cycloaddition becomes possible only when the s-Z-conformation of vinylketene is significantly populated, the presence of bromine substituents in this substrate is crucial in determining the [2+2] or [4+2] mechanisms. For unsubstituted vinylketenes, the barrier connecting the s-E- to the s-Z-conformation is too high to be easily overcome. Thus, the s-Z-structure has a low population and the [2+2] mechanism is favoured. In the case of alpha-bromo vinylketenes (especially the beta-methyl-substituted ones), this barrier can be surmounted and the [4+2] mechanism becomes available.