Enantioselective Desymmetrization Triggered by Iminium-Enamine Activation: Access to Complex Cyclohepta[b]indoles.

The expeditious construction of complex molecules having multiple stereocentres is highly desirable in organic chemistry. In the present communication, we report the development of an organocatalytic asymmetric desymmetrization of prochiral enal-tethered cyclohexadienones via the C3-selective Friedel-Crafts alkylation of indoles triggered by LUMO-lowering iminium activation/HOMO-raising enamine activation. The reaction provides access to bicyclic enones, which further undergo acid-mediated intramolecular annulation from C2-position to afford highly strained cyclohepta[b]indoles with five contiguous stereocentres and three new C-C bonds in excellent enantioselectivity and diastereoselectivity.

Rh-Catalyzed diastereoselective desymmetrization of enone tethered-cyclohexadienones via tandem arylative cyclization.

The rhodium-catalyzed arylative cyclization of enone tethered-cyclohexadienones has been developed with high efficiency, thus providing cis-fused bicyclic enones in good yields and with excellent diastereoselectivities. Furthermore, this mild transformation has a broad range of substrate scope and excellent functional group tolerance. In addition, bicyclic products have an enone functionality, which can be a synthetically valuable handle for further transformations.

Organocatalytic enantioselective desymmetrization of enal-tethered cyclohexane-1,3-diones.

Organocatalytic asymmetric desymmetrization of prochiral cyclohexane-1,3-diones has been demonstrated through the merging of iminium and enamine activation. The tandem annulation reaction proceeds through a sequential oxa-Michael addition/intramolecular aldol reaction/[1,3]-amino oxetane rearrangement pathway. Mechanistic study using an 18O-water experiment suggests oxetane rearrangement instead of direct dehydration. The formation of other competing Rauhut-Currier products via alkoxy-elimination was not observed.

Site-selective and stereoselective transformations on p-quinols & p-quinamines.

The intermolecular transformation of simple substrates into highly functionalized scaffolds with multiple stereogenic centers is an attractive strategy in modern organic synthesis. Prochiral 2,5-cyclohexadienones, being stable and easily accessible, are privileged key building blocks for the synthesis of complex molecules and bioactive natural products. In particular, p-quinols and p-quinamines are important subclasses of cyclohexadienones, having both nucleophilic and electrophilic sites, and can undergo various intermolecular cascade annulations via formal cycloadditions and other transformations. This article highlights the recent developments of intermolecular transformations on p-quinols and p-quinamines along with plausible reaction mechanisms. We hope that this review will inspire the readers to explore the new potential applications of these unique prochiral molecules.

Solvent-Mediated Enantioselective Rauhut-Currier Cyclization via Iminium and Enamine Activation.

In this work, we have developed an unconventional and highly enantioselective solvent-promoted Rauhut-Currier cyclization of enal-tethered cyclohexadienone by exploiting the reactivity of a simple Jørgensen-Hayashi catalyst through the merging of iminium and enamine activation. This asymmetric desymmetrization reaction has broad substrate scope in good yields with high to excellent enantioselectivity. DFT calculations suggest that the elimination of the alkoxy group is the rate-limiting step and that it proceeds through proton abstraction by solvent instead of a direct 1,3-proton shift.