The α-effect in cyclic secondary amines: new scaffolds for iminium ion accelerated transformations

Five-membered secondary amine heterocycles containing all alpha-heteroatom were prepared and shown to be ineffective as catalysts for the iminium ion catalysed Diels-Alder reaction between cinnamaldehyde and cyclopentadiene. Their six-membered counterparts proved to be highly active catalysts. In stark contrast, the catalytic activity observed when comparing the non alpha-heteroatom cyclic amines proline methyl ester and methyl pipecolinate showed the five-membered ring amine was significantly more active. Concurrent density functional theoretical calculations suggest a rationale for the observed trends in reactivity, highlighting that LUMO activation through all iminium ion intermediate plays a key role ill catalytic activity. (C) 2009 Elsevier Ltd. All rights reserved.