Organophotocatalysis: Insights into the Mechanistic Aspects of Thiourea‐Mediated Intermolecular [2+2] Photocycloadditions

Mechanistic investigations of the intermolecular [2+2] photocycloaddition of coumarin with tetramethylethylene mediated by thiourea catalysts reveal that the reaction is enabled by a combination of minimized aggregation, enhanced intersystem crossing, and altered excited‐state lifetime(s). These results clarify how the excited‐state reactivity can be manipulated through catalyst–substrate interactions and reveal a third mechanistic pathway for thiourea‐mediated organo‐photocatalysis.     

Enantioselective Organocatalytic Construction of Spiroindane Derivatives by Intramolecular Friedel–Crafts‐Type 1,4‐Addition

The highly enantioselective organocatalytic construction of spiroindanes containing an all‐carbon quaternary stereocenter by intramolecular Friedel–Crafts‐type 1,4‐addition is described. The reaction was catalyzed by a cinchonidine‐based primary amine and accelerated by water and p‐bromophenol. A variety of spiro compounds containing quaternary stereocenters were obtained with excellent enantioselectivity (up to 95 % ee). The reaction was applied to the asymmetric formal synthesis of the spirocyclic natural products (?)‐cannabispirenones A and B.     

Construction of Chiral Cyclic Compounds Enabled by Enantioselective Photocatalysis

Chiral cyclic molecules are some of the most important compounds in nature, and are widely used in the fields of drugs, materials, synthesis, etc. Enantioselective photocatalysis has become a powerful tool for organic synthesis of chiral cyclic molecules. Herein, this review summarized the research progress in the synthesis of chiral cyclic compounds by photocatalytic cycloaddition reaction in the past 5 years, and expounded the reaction conditions, characters, and corresponding proposed mechanism, hoping to guide and promote the development of this field.     

Catalytic Enantioselective Formal (4+2) Cycloaddition by Aldol–Aldol Annulation of Pyruvate Derivatives with Cyclohexane‐1,3‐Diones to Afford Functionalized Decalins

The decalin structure is found in bioactive molecules. We have developed catalytic enantioselective formal (4+2) cycloaddition reactions via aldol–aldol cascade reactions between pyruvate‐derived diketoester derivatives and cyclohexane‐1,3‐dione derivatives that afford highly functionalized decalin derivatives. The reactions were performed using a quinidine‐derived catalyst under mild conditions. Decalin derivatives bearing up to six chiral carbon centers including tetrasubstituted carbon centers were synthesized with high diastereo‐ and enantioselectivities. Five to six stereogenic centers were generated from achiral molecules with the formation of two C?C bonds in a single transformation resulting in the formation of the decalin system.     

Asymmetric Synthesis of Spiropyrazolones by Sequential Organo‐ and Silver Catalysis

A stereoselective one‐pot synthesis of spiropyrazolones through an organocatalytic asymmetric Michael addition and a formal Conia‐ene reaction has been developed. Depending on the nitroalkene, the 5‐exo‐dig‐cyclization could be achieved by silver‐catalyzed alkyne activation or by oxidation of the intermediate enolate. The mechanistic pathways have been investigated using computational chemistry and mechanistic experiments.     

Catalytic Enantioselective Aza‐Piancatelli Rearrangement

An efficient organocatalytic enantioselective aza‐Piancatelli rearrangement is disclosed. The powerful process provides rapid access to valuable chiral 4‐amino‐2‐cyclopentenone building blocks from readily available 2‐furfurylcarbinols with excellent chemo‐, enantio‐, and diastereoselectivities under mild reaction conditions.     

Carbamate‐Catalyzed Enantioselective Bromolactamization

A highly facile, efficient, and enantioselective bromolactamization of olefinic amides was effected by a carbamate catalyst and ethanol additive. The amide substrates underwent N‐cyclization predominantly to give a diverse range of enantioenriched bromolactam products containing up to two stereogenic centers.     

Enantioselective Trifluoromethylthiolating Lactonization Catalyzed by an Indane‐Based Chiral Sulfide

Enantioselective trifluoromethylthiolation, especially of alkenes, is a challenging task. In this work, we have developed an efficient approach for enantioselective trifluoromethylthiolating lactonization by designing an indane‐based bifunctional chiral sulfide catalyst and a shelf‐stable electrophilic SCF₃ reagent. The desired products were formed with diastereoselectivities of >99:1 and good to excellent enantioselectivities. The transformation represents the first enantioselective trifluoromethylthiolation of alkenes and the first enantioselective trifluoromethylthiolation that is enabled by a catalyst with a Lewis basic sulfur center.     

Synthesis of α‐Stereogenic Amides and Ketones by Enantioselective Conjugate Addition of 1,4‐Dicarbonyl But‐2‐enes

Constructing α‐stereogenic amides and ketones : The highly regioselective and enantioselective conjugate addition of 1,3‐dicarbonyl compounds to 1,4‐dicarbonyl but‐2‐enes has been developed with the chiral bicyclic guanidine as catalyst (ee values up to 97 %; see scheme).

     

Organocatalytic Enantioselective Synthesis of 1,4‐Dioxanes and Other Oxa‐Heterocycles by Oxetane Desymmetrization

A new asymmetric synthesis of chiral 1,4‐dioxanes and other oxa‐heterocycles has been developed by means of organocatalytic enantioselective desymmetrization of oxetanes. This mild process proceeds with exceedingly high efficiency and enantioselectivity to establish the quaternary stereocenters. This method complements the existing, yet limited, strategies for the synthesis of these oxa‐heterocycles.     

Tandem Organocatalysis and Photocatalysis: An Anthraquinone‐Catalyzed Indole‐C3‐Alkylation/Photooxidation/1,2‐Shift Sequence

Quinones exhibit orthogonal ground‐ and excited‐state reactivities and are therefore highly suitable organocatalysts for the development of sequential catalytic processes. Herein, the discovery of an anthraquinone‐catalyzed thermal indole‐C3‐alkylation with benzylamines is described, which can be combined sequentially with a new visible‐light‐driven catalytic photooxidation/1,2‐shift reaction. The one‐flask tandem process converts indoles into 3‐benzylindole intermediates, which are further transformed into new fluorescent 2,2‐disubstituted indoline‐3‐one derivatives.     

Enantioselective Intramolecular Desymmetric α‐Addition of Cyclohexanone to Propiolamide Catalyzed by Sodium L‐Prolinate

An enantioselective desymmetric nucleophilic α‐addition of cyclohexanone to propiolamide has been developed through a 6‐exo‐dig cyclization reaction. By employing simple and readily available L‐proline sodium salt as a bifunctional catalyst, a series of chiral 6,6‐bicyclic bridged products bearing morphan scaffold have been isolated in good yields and excellent enantioselectivities. Density functional theory (DFT) calculations elucidated the origins of the enantioselectivity and regioselectivity of this transformation. A salt bridge that links the amide carbonyl group with proline carboxylate in the transition state was proven to be the driving force for the induction of excellent enantioselectivity.