A diastereoselective cascade annulation between allenoates and in-situ generated isoquinoline N-oxides generating sp 3 -rich bridged polycyclic heterocycles is disclosed. The reaction proceeds through an unprecedented non-rearomatized rearrangement and allows access to a broad range of bridged heterocycles in 38−93% yields with excellent functional group tolerance and high diastereoselectivity. Density functional theory calculations provided key insights into the possible reaction pathway and the stereoselectivity of this procedure.N itrogen heterocycles play an important role in several fields such as drug development, agrochemicals, dyes, and polymers. 1 The development of new synthetic methods that can significantly increase the molecular complexity allows improvements in efficiency and cost-effectiveness, thus boosting the drug discovery and development process. 2 Cascade cyclizations are among the most powerful tools in organic synthesis for generating complex polycyclic molecular scaffolds in high yields and stereoselectivity in a single operation. 3 Recently, we and others have investigated cascade reactions involving o-alkynylbenzaldoximes for the synthesis of functionalized isoquinolines. 4 However, approaches that can be implemented for the synthesis of complex three-dimensional bridged heterocycles by perturbation of the aromaticity of the isoquinoline core are rare because of the inherently low reactivity of aromatic systems as well as the tendency of the formed intermediates to return to their initial aromatic state. 5 One rare exception was reported by Wu on the basis of the reaction of o-alkynylbenzaldoximes and arynes leading to 2-oxa-6-azabicyclo[3.2.2]nona-6,8-diene derivatives (Scheme 1a). 6 In another example, Fan developed a direct and efficient one-pot method for the synthesis of multisubstituted oxocino[4,3,2-cd]indoles from o-alkynylanilines and o-alkynylbenzaldoximes. The reaction proceeds via the oxidative dearomatization of o-alkynylanilines, the silvercatalyzed [3+3] cycloaddition with o-alkynylbenzaldoximes, the subsequent thermal radical skeletal rearrangement, and aromatization (Scheme 1b). 7 In both examples, the final rearrangement proceeds through C−O bond formation leading