Gd(III)-Catalyzed Regio-, Diastereo-, and Enantioselective [4 + 2] Photocycloaddition of Naphthalene Derivatives.

Catalytic asymmetric dearomatization (CADA) reactions have evolved into an efficient strategy for accessing chiral polycyclic and spirocyclic scaffolds from readily available planar aromatics. Despite the significant developments, the CADA reaction of naphthalenes remains underdeveloped. Herein, we report a Gd(III)-catalyzed asymmetric dearomatization reaction of naphthalene with a chiral PyBox ligand via visible-light-enabled [4 + 2] cycloaddition. This reaction features application of a chiral Gd/PyBox complex, which regulates the reactivity and selectivity simultaneously, in excited-state catalysis. A wide range of functional groups is compatible with this protocol, giving the highly enantioenriched bridged polycycles in excellent yields (up to 96%) and selectivity (up to >20:1 chemoselectivity, >20:1 dr, >99% ee). The synthetic utility is demonstrated by a 2 mmol scale reaction, removal of directing group, and diversifications of products. Preliminary mechanistic experiments are performed to elucidate the reaction mechanism.

Photo-induced intramolecular dearomative [5 + 4] cycloaddition of arenes for the construction of highly strained medium-sized-rings.

Medium-sized-ring compounds have been recognized as challenging synthetic targets in organic chemistry. Especially, the difficulty of synthesis will be augmented if an E-olefin moiety is embedded. Recently, photo-induced dearomative cycloaddition reactions that proceed via energy transfer mechanism have witnessed significant developments and provided powerful methods for the organic transformations that are not easily realized under thermal conditions. Herein, we report an intramolecular dearomative [5 + 4] cycloaddition of naphthalene-derived vinylcyclopropanes under visible-light irradiation and a proper triplet photosensitizer. The reaction affords dearomatized polycyclic molecules possessing a nine-membered-ring with an E-olefin moiety in good yields (up to 86%) and stereoselectivity (up to 8.8/1 E/Z). Detailed computational studies reveal the origin behind the favorable formation of the thermodynamically less stable isomers. Diverse derivations of the dearomatized products have also been demonstrated.

Enantioselective Synthesis of Cyclobutane Derivatives via Cascade Asymmetric Allylic Etherification/[2 + 2] Photocycloaddition.

Chiral cyclobutane presents as a popular motif in natural products and biologically active molecules, and its derivatives have been extensively used as key synthons in organic synthesis. Herein, we report an efficient synthetic method toward enantioenriched cyclobutane derivatives. The reaction proceeds in a cascade fashion involving Ir-catalyzed asymmetric allylic etherification and visible-light induced [2 + 2] cycloaddition. Readily available branched allyl acetates and cinnamyl alcohols are directly used as the substrates under mild reaction conditions, providing a broad range of chiral cyclobutanes in good yields with excellent diastereo- and enantioselectivities (up to 12:1 dr, >99% ee). It is worth noting that all substrates and catalysts were simultaneously added without any separated step in this approach. The gram-scale reaction and diverse transformations of product further enhance the potential utility of this method.

Visible-Light-Induced Dearomatization of Indoles/Pyrroles with Vinylcyclopropanes: Expedient Synthesis of Structurally Diverse Polycyclic Indolines/Pyrrolines.

Visible-light-induced cycloaddition reactions initiated via energy-transfer processes have recently evolved as powerful methods for the construction of strained cyclic molecules that are not easily accessed using known ground-state synthetic methods. Particularly, the reactions initiated by the excitation of aromatic rings provide an alternative solution to the direct transformations of aromatic feedstocks under the scheme of dearomatization. Vinylcyclopropanes (VCPs) are well-known reagents in radical clock experiments, working as a probe to detect transient radical intermediates. However, the synthetic applications in this regard still remain limited due to uncontrollable selectivities. Herein, we report visible-light-induced dearomatization of indole- or pyrrole-tethered VCPs, in which several competitive reaction pathways, including [5 + 2], [2 + 2], interrupted [5 + 2], and [5 + 4] cycloadditions, can be well regulated by engineering substrate structures and tuning reaction conditions. The reaction mechanism has been explored by combined experimental and computational investigations. These reactions provide a convenient method to synthesize structurally diverse polycyclic molecules with high efficiency and good selectivity.

Photoredox-Catalyzed Intermolecular Hydroalkylative Dearomatization of Electron-Deficient Indole Derivatives.

Dearomatization of indole derivatives offers a straightforward approach to access diverse indolines. To date, the corresponding dearomative transformations involving electron-deficient indoles are limited. Herein, we report a one-electron strategy for dearomatization of electron-deficient indoles via a photoredox-catalyzed hydroalkylation employing commercially available glycine derivatives as the hydrofunctionalization reagents. Followed by DBU-mediated lactamization, structurally appealing lactam-fused indolines are obtained in good to excellent yields with exclusive selectivity.

Intermolecular Dearomatization of Naphthalene Derivatives by Photoredox-Catalyzed 1,2-Hydroalkylation.

An intermolecular hydroalkylative dearomatization of naphthalenes with commercially available α-amino acids is achieved via visible-light photoredox catalysis. With an organic photocatalyst, a series of multi-substituted 1,2-dihydronaphthalenes are obtained in good-to-excellent yields. Intriguingly, by tuning the substituents at the C2 position of naphthalenes, formal dearomative [3+2] cycloadditions occur exclusively via a hydroalkylative dearomatization-cyclization sequence. This overall redox-neutral method features mild reaction conditions, good tolerance of functionalities, and operational simplicity. Diverse downstream elaborations of the products are demonstrated. Preliminary mechanistic studies suggest the involvement of a radical-radical coupling pathway.