A metal-free domino reaction for the synthesis of a new family of fused bicyclic 1,4-diazepanes and 1,5-diazocanes has been developed. The reaction involves the use of N,N′-dialkylated 1,n-diamines as the nitrogen source, through-space orbital interactions between the two nitrogen atoms as the reactivity director element, and an activated skipped diyne as the reactive platform. A key Morita-Baylis-Hillman-like reaction allows the formation of 1,4-diazepanes and 1,5-diazocanes (medium-sized diazoheterocycles). These structures incorporate a 1,n-diazocycle fused to a Î3-butenolide ring and different functionalities to be used as convenient handles for further complexity generation. The good efficiency of this reaction and its simple experimental protocol make this process an excellent candidate for the fast construction of structure-focused libraries based on this fused bicyclic motif. © 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. ; This research was supported by the Spanish Spanish Ministerio de Ciencia e Innovación (MICINN), the European Regional Development Fund (RDF) (CTQ2008-06806-C02-02), and the Spanish Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (MSC ISCIII) (RETICS RD06/0020/1046) and the Fundación Canaria de Investigación y Salud (FUNCIS) (PI 43/09). ; Peer Reviewed