Light-Mediated Chiral Phosphate Catalysis for Asymmetric Dicarbofunctionalization of Enamides

Abstract

A light-mediated asymmetric dicarbofunctionalization of enamides with carboxylic-acid-derived redox-active esters (RAEs) and indoles has been established by using chiral lithium phosphate catalysis in the presence or absence of photoredox catalyst. This reaction features mild reaction conditions and broad substrate scopes, delivering a wide range of highly functionalized chiral amine derivatives. Mechanistic studies suggest that chiral lithium phosphate can serve as a pocket to accelerate the aggregation of enamide and RAE through hydrogen-bonding and coordination interaction, enabling the formation of a charge-transfer complex (CTC). Either enamide or CTC can be excited by direct irradiation or Ru­(II)-mediated photosensitization to furnish chiral iminium intermediates for the asymmetric Friedel–Crafts reaction of indole.

Palladium‐Catalyzed Regio‐, Diastereo‐, and Enantioselective 1,2‐Arylfluorination of Internal Enamides

“…More recently, the transition metal‐catalyzed enantioselective dicarbofunctionalization of N ‐vinyl amide enabled by the radical relay strategy represents an alternative advance to form C−C bond, whereas the radical intermediate generated in situ could only add to the terminal position of enamide (Scheme 1 b). [9–13] As such, the highly regio‐, diastereo‐, and enantioselective transition metal‐catalyzed intermolecular difunctionalization of internal enamide with C−C bond formation still remains a formidable challenge.…”

“…[a] Reaction conditions: 1 a (0.2 mmol), 2 a (2.0 equiv, 0.4 mmol), Selectfluor (4.0 equiv, 0.8 mmol), Pd(OAc) 2 (5.0 mol %, 0.01 mmol), ligand (6.0 mol %, 0.012 mmol), 4-(benzyloxy)benzoic acid (40 mol %, 0.08 mmol), DCM: strategy represents an alternative advance to form CÀC bond, whereas the radical intermediate generated in situ could only add to the terminal position of enamide (Scheme 1 b). [9][10][11][12][13] As such, the highly regio-, diastereo-, and enantioselective transition metal-catalyzed intermolecular difunctionalization of internal enamide with CÀC bond formation still remains a formidable challenge. b-Fluoroamine represents an important class of enzyme inhibitors, antitumor and antibacterial reagents.…”

Asymmetric Photocatalysis Enabled by Chiral Organocatalysts

“…applied the same strategy to achieve photocatalytic enantioselective enamide difunctionalization (Scheme 88). [156] A photoredox catalyst was essential in this visible‐light‐induced reaction, but enamide could also work as a photosensitizer to initiate the reaction under UV irradiation. A wide array of enantioenriched amine derivatives was obtained in 45–85 % yields and 76–88 % ee.…”

Metal-free, visible-light induced enantioselective three-component dicarbofunctionalization and oxytrifluoromethylation of enaminesviachiral phosphoric acid catalysis

“… 7,8 Combining with organocatalysis, 9 Lewis acid catalysis, 10 transition metal catalysis 11 and even enzymatic catalysis, 12 the development of asymmetric photocatalysis has attracted increasing attention of organic chemists. Until now, only a few examples of the photocatalytic asymmetric three-component alkene difunctionalization enabled by photoredox and metal dual catalysis have been reported, 13 which deserves to be further explored. Chiral phosphoric acids (CPAs), as powerful bifunctional organic catalysts, 14 have been employed in visible-light photoredox catalyzed reactions by Jiang 15 and others, 16 which proceeded via different enantioselective processes to control the stereoselectivity of the reactions.…”