DOI: 10.1002/ejoc.201600720 Full Paper Benzo-Fused Rings Palladium-Catalysed Carbo- and Hydroamination of Allenyl Ethers and Aminoallenes: Available Entry to Nitrogen- Containing Benzo-Fused Rings Silvia Gazzola, [a] Egle M. Beccalli* [b] Alice Bernasconi, [b] Tea Borelli, [a] Gianluigi Broggini, [a] and Alberto Mazza [b] Abstract: The Pd-catalysed reactions of allenyl ethers and allenylamines derived from commercially available o-amino- phenols and o-nitroaniline have been studied. Using a wide va- riety of aryl- and heteroaryl halides, carboamination of the allenes led to sequential C–C and C–N bond formation. Both carbo- and hydroamination processes resulted in the formation Introduction The remarkable reactivity of allenes, which are more reactive than other unsaturated groups, has attracted considerable at- tention, in particular under transition-metal catalysis. [1] Intramo- lecular carbo- [2] and hydroamination [3] processes are fruitful methods for obtaining nitrogen-containing heterocycles. More- over, the use of allenes as substrates in such reactions allows one of the allene double bonds to be preserved for further transformations. The limited number of synthetic applications of Pd-catalysed hydroamination reactions involving allenes re- ported in literature, [4] the positive results previously reported by our research group on the transition-metal-catalysed reac- tions of allenamides [5] and our ongoing interest in amination processes [6] prompted us to increase the range of heterocycles available for the synthesis of biologically active compounds. Considering the allene derivatives arising from commercially available o-aminophenols and o-phenylenediamines as useful substrates, we proposed to synthesize vinyl-substituted benz- oxazoles and -imidazoles, two scaffolds endowed with various biological activities, for example, a recently synthesized sub- strate shows potential for the treatment of Alzheimer's dis- ease. [7] Moreover, benzoxazole derivatives have been classified as an HIV reverse transcriptase inhibitor, [8a] orexin-1 receptor antagonist, [8b] estrogen receptor- agonist [8c] and Rho kinase [a] Dipartimento di Scienza e Alta Tecnologia, Università degli Studi dell'Insubria, Via Valleggio 9, 22100 Como, Italy E-mail: gianluigi.broggini@uninsubria.it [b] DISFARM, Sezione di Chimica Generale e Organica “A. Marchesini”, Università degli Studi di Milano, Via Venezian 21, 20133 Milano, Italy E-mail: egle.beccalli@unimi.it www.disfarm.unimi.it Supporting information and ORCID(s) from the author(s) for this article are available on the WWW under http://dx.doi.org/10.1002/ejoc.201600720. Eur. J. Org. Chem. 0000, 0–0 © 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 1 of nitrogen-containing benzo-fused rings. In the case of amino- allenes arising from o-phenylenediamine, the regioselectivity of the cyclization step was strongly dependent on the protecting group tethered to the nitrogen atoms, allowing the formation of five- and seven-membered rings. inhibitors, [8d] and have also been evaluated for their antimicro- bial and antitubercular activity. [8e–8h] Benzoxazoles are also con- tained in the skeleton of boxazomycin antibiotics. [9] Benzimid- azoles have also been extensively used in medicinal chemistry due to their ability to cross the blood/brain barrier. [10] Several derivatives, such as 2-styrylbenzimidazoles, have been devel- oped to combat antibiotic resistance and some of them exhibit antibacterial, antifungal and antiparasitic properties. [11] Benz- oxazoles such as UK-1 and benzimidazoles such as ABT-888 and gastrazole possess antitumour activity in the treatment of a va- riety of cancers, acting as topoisomerase inhibitors (Figure 1). [12] For these reasons, although several methods for the synthesis of benzoxazoles and -imidazoles have been reported in the lit- erature, [13–20] the development of new procedures remains of considerable interest. Figure 1. Gastrazole (JB95008), ABT-888 and UK-1 anticancer agents showing antimicrobial and antitubercular properties.