Ring Contraction of Saturated Cyclic Amines and Rearrangement of Acyclic Amines Through Their Corresponding Hydroxylamines

Compared to modifications at the molecular periphery, skeletal adjustments present greater challenges. Within this context, skeletal rearrangement technology stands out for its significant advantages in rapidly achieving structural diversity. Yet, the development of this technology for ring contraction of saturated cyclic amines remains exceedingly rare. While most existing methods rely on specific substitution patterns to achieve ring contraction, there is a persistent demand for a more general strategy for substitution‐free cyclic amines. To address this issue, we report a B(C6F5)3‐catalyzed skeletal rearrangement of hydroxylamines with hydrosilanes. This methodology, when combined with the N‐hydroxylation of amines, enables the regioselective ring contraction of cyclic amines and proves equally effective for rapid reorganization of acyclic amine skeletons. By this, the direct scaffold hopping of drug molecules and the strategic deletion of carbon atoms are achieved in a mild manner. Based on mechanistic experiments and density functional theory calculations, a possible mechanism for this process is proposed. A novel rearrangement promoted by a B(C6F5)3‐hydrosilane pair enables the regioselective ring contraction of saturated cyclic hydroxylamines as well as the skeletal reorganization of acyclic derivatives. The method overcomes the limitations of traditional uncatalyzed Stieglitz rearrangements, allowing for swift structural transformations between different types of amines. The mechanism of this rearrangement is investigated by control experiments and DFT calculations.