The incorporation of amines into organic scaffolds remains a central goal in synthetic organic chemistry, with broad implications for the construction of pharmaceuticals, agrochemicals, and natural products. In particular, nitrogen heterocycles are abundantly prevalent in bioactive molecules, with 82% of newly approved small-molecule drugs over the past decade containing at least one such moiety.[1] Carboamination reactions, which introduce both carbon and nitrogen units across unsaturated C–C bonds, offer a powerful strategy for assembling complex nitrogen-containing architectures. Established methodologies for alkene carboamination typically rely on tethered nucleophiles to enable intramolecular cyclizations, often under palladium, copper, or nickel catalysis, to afford azaheterocycles. In contrast, intermolecular three-component variants employ directing groups to control regioselectivity, granting access to substituted aliphatic amines in a modular fashion.[2]

We have extended this reactivity paradigm to the carboamination of enynes, providing a new route to multi-substituted nitrogen-containing allenes. Allenes are highly versatile intermediates in organic synthesis, due to their unique axial chirality and electronic properties, and they also feature in a range of natural products and functional materials.[3] Nevertheless, nitrogen-functionalized allenes, particularly complex multisbubstituted allenes, remain largely underexplored due to the lack of general and efficient synthetic routes. A streamlined and modular method to access such scaffolds from simple and readily available starting materials is therefore highly desirable.

Recent advances in transition-metal-catalyzed 1,4-functionalization of unactivated enynes highlight the potential of this strategy to access diverse allene frameworks in a concise and regioselective manner.[4] Building on this, we developed an intermolecular, Pd-catalyzed three-component carboamination of conjugated enynes. This transformation enables efficient, modular synthesis of multi-substituted nitrogen-containing allenes, while avoiding common side reactions such as Buchwald–Hartwig amination, double amination, or hydroamination.[5] Notably, the method applies to dihydropyrrole synthesis, highlighting its broader utility in heterocycle construction.

[1] C. M. Marshall, J. G. Federice, C. N. Bell, P. B. Cox, J. T. Njardarson, J. Med. Chem. 2024, 67, 11622.

[2] S. K. Nanda, R. Mallik, Asian J. Org. Chem. 2022, 11, e202100552.

[3] S. Yu, S. Ma, Angew. Chem. Int. Ed. 2012, 51, 3074.

[4] L. Fu, S. Greßies, P. Chen, G. Liu, Chin. J. Chem. 2020, 38, 91.

[5] Manuscript in preparation.