Organic Chemistry

Photochemical Synthesis of 1-Aminonorbornanes via Strain-Driven, Formal [3+2] Cycloadditions



This report describes a new route toward 1‑aminonorbornanes via strain-driven, visible light-mediated formal [3+2] cycloadditions with aminocyclopropanes. Lewis acidic salts (LiBF4, ZnCl2) were found to facilitate the oxidation of a variety of amine-containing heterocycles, and consequently, these additives led to improved conversion and isolated yields. This operationally-simple method tolerates a variety of functional handles (e.g. alcohols, protected amines), can generate optically-pure products through diastereoselective variations, and affords entry to unique chemical space through the diversity of accessible substitution patterns. Providing flexible access to 1-aminonorbornanes is expected to benefit modern drug design and development efforts seeking to incorporate more sp3-rich motifs into lead scaffods. Further, gram-scale operation proceeds smoothly in continuous flow, suggesting that this chemistry can be readily translated beyond the academic- or discovery-scales.


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