Influence of Non-Covalent Interactions in the Exo- and Regioselectivity of Aza-Diels-Alder Reactions: Experimental and DFT Calculations.

A systematic experimental and theoretical study of the intermolecular Aza-Diels-Alder reaction using 5-aminopyrrole as a building block shows that the commonly accepted endo selectivity, ruled by controversial secondary orbital interactions, are overcome by non-covalent interactions affording to the unusual exo adduct. Additionally, the regioselectivity is also influenced for such interactions. The starting materials are easily prepared, and the use of water as the solvent is a great achievement for the development of cleaner synthetic methodologies.