Synthesis of Functionalized Hexahydrocarbazoles by Beckmann Elimination and Nucleophile-Intercepted Beckmann Fragmentation.

The Beckmann elimination and nucleophile-intercepted Beckmann fragmentation (NuBFr) of oximes starting from regioisomeric indolinyl bicyclic ketones lead to products that are subjected to further synthetic manipulations and ultimately result in the stereospecific formation of densely functionalized hexahydrocarbazoles. The Pd-catalyzed Suzuki-Miyaura cross-coupling reaction of a key alkenyl bromide intermediate with various boronic acids gives arylated products.

Regiodivergent (3 + 2) annulation reactions of oxyallyl cations.

We report a new method for the regiodivergent dearomative (3 + 2) reaction between 3-substituted indoles and oxyallyl cations. Access to both regioisomeric products is possible and is contingent on the presence or absence of a bromine atom on the substituted oxyallyl cation. In this way, we are able to prepare molecules that contain highly-hindered, stereodefined, vicinal, quaternary centers. Detailed computational studies employing energy decomposition analysis (EDA) at the DFT level establishes that regiochemical control arises from either reactant distortion energy or orbital mixing and dispersive forces, depending on the oxyallyl cation. Examination of the Natural Orbitals for Chemical Valence (NOCV) confirms that indole acts as the nucleophilic partner in the annulation reaction.