Recent developments in enantioselective photocatalysis

Abstract

Enantioselective photocatalysis has rapidly grown into a powerful tool for synthetic chemists. This review describes the various strategies for creating enantioenriched products through merging enantioselective catalysis and photocatalysis, with a focus on the most recent developments and a particular interest in the proposed mechanisms for each. With the aim of understanding the scope of each strategy, to help guide and inspire further innovation in this field.

Keywords: enantioenrichment; enantionselective catalysis; enantioselective photocatalysis; photocatalysis; photochemistry.

Scheme 1

Amine/photoredox-catalysed α-alkylation of aldehydes with alkyl bromides bearing electron-withdrawing groups.

Scheme 2

Amine/HAT/photoredox-catalysed α-functionalisation of aldehydes using alkenes.

Scheme 3

Amine/cobalt/photoredox-catalysed α-functionalisation of ketones and THIQs.

Scheme 4

Amine/photoredox-catalysed α-functionalisation of aldehydes or ketones with imines. (a) Using ketones with 2-substituted indoles. (b) Using ketones or aldehydes with glycine derivatives.

Scheme 5

Bifunctional amine/photoredox-catalysed enantioselective α-functionalisation of aldehydes.

Scheme 6

Bifunctional amine/photoredox-catalysed α-functionalisation of aldehydes using amine catalysts via EDA complexes and direct excitation of intermediates.

Scheme 7

Amine/photoredox-catalysed RCA of iminium ion intermediates. (a) Synthesis of quaternary stereocentres using benzodioxole derivatives or tertiary amines. (b) Synthesis of 1,4-dicarbonyls using carboxylic acids.

Scheme 8

Bifunctional amine/photoredox-catalysed RCA of enones in a radical chain reaction initiated by an intramolecular EDA complex.

Scheme 9

Bifunctional amine/photoredox-catalysed RCA reactions of iminium ions with different radical precursors. (a) Silanes. (b) Toluene derivatives. (c) Alkyl and acyl DHP derivatives.

Scheme 10

Bifunctional amine/photoredox-catalysed radical cascade reactions between enones and alkenes with attached nucleophilic groups. (a) Alkenes with attached carboxylic acid or alcohol. (b) Allenes with attached carboxylic acid.

Scheme 11

Amine/photocatalysed photocycloadditions of iminium ion intermediates. (a) External photocatalyst used as triplet sensitiser with enals and dienes. (b) Bifunctional amine catalyst used with enones and alkenes.

Scheme 12

Amine/photoredox-catalysed addition of acrolein (94) to iminium ions.

Scheme 13

Dual NHC/photoredox-catalysed acylation of THIQs.

Scheme 14

NHC/photocatalysed spirocyclisation via photoisomerisation of an extended Breslow intermediate.

Scheme 15

CPA/photoredox-catalysed aza-pinacol cyclisation.

Scheme 16

CPA/photoredox-catalysed Minisci-type reaction between azaarenes and α-amino radicals.

Scheme 17

CPA/photoredox-catalysed radical additions to azaarenes. (a) α-Amino radical or ketyl radical addition to 2-vinylazaarenes. (b) Minisci-type reaction using redox-active esters and isoquinolines. (c) Radical cascade reaction using α-carbonyl radicals with enamides.

Scheme 18

CPA/photoredox-catalysed reduction of azaarene-derived substrates. (a) Reduction of ketones. (b) Extension to deuteration of ketones and alkyl halides.

Scheme 19

CPA/photoredox-catalysed radical coupling reactions of α-amino radicals with α-carbonyl radicals. (a) Using α-bromoketones. (b) Using α-chloro-2-oxindoles or 1,2-diketones.

Scheme 20

CPA/photoredox-catalysed Povarov reaction.

Scheme 21

CPA/photoredox-catalysed reactions with imines. (a) Decarboxylative imine generation followed by Povarov reaction with an enamide. (b) Imine trapped by intramolecular nucleophile and intermolecular nucleophile.

Scheme 22

Bifunctional CPA/photocatalysed [2 + 2] photocycloadditions.

Scheme 23

PTC/photocatalysed oxygenation of 1-indanone-derived β-keto esters.

Scheme 24

PTC/photoredox-catalysed perfluoroalkylation of 1-indanone-derived β-keto esters via a radical chain reaction initiated by an EDA complex.

Scheme 25

Bifunctional hydrogen bonding/photocatalysed intramolecular [2 + 2] photocycloadditions of quinolones.

Scheme 26

Bifunctional hydrogen bonding/photocatalysed intramolecular RCA cyclisation of a quinolone.

Scheme 27

Bifunctional hydrogen bonding/photocatalysed intramolecular [2 + 2] photocycloadditions of quinolones.

Scheme 28

Bifunctional hydrogen bonding/photocatalysed [2 + 2] photocycloaddition reactions. (a) First use of the thioxanthone-based bifunctional catalyst for an intramolecular cycloaddition. (b) Intermolecular cycloaddition of pyridines and acetylenedicarboxylates using a xanthone-based photocatalyst. (c) Intermolecular cycloaddition of quinolones with electron-deficient alkenes using a thioxanthone-based photocatalyst. (d) Intramolecular cycloaddition of quinolones with attached alkenes or allenes using a thioxanthone-based photocatalyst.

Scheme 29

Bifunctional hydrogen bonding/photocatalysed deracemisation of allenes.

Scheme 30

Bifunctional hydrogen bonding/photocatalysed deracemisation reactions. (a) Deracemisation of sulfoxides. (b) Photochemical rearrangement followed by photocatalysed deracemisation of the resulting cyclopropane products.

Scheme 31

Bifunctional hydrogen bonding/photocatalysed intramolecular [2 + 2] photocycloaddition of coumarins.

Scheme 32

Bifunctional hydrogen bonding/photocatalysed [2 + 2] photocycloadditions of quinolones. (a) Intramolecular cycloaddition of quinolones. (b) Intermolecular cycloaddition of quinolones and maleimides.

Scheme 33

Hydrogen bonding/photocatalysed formal arylation of benzofuranones.

Scheme 34

Hydrogen bonding/photoredox-catalysed dehalogenative protonation of α,α-chlorofluoro ketones.

Scheme 35

Hydrogen bonding/photoredox-catalysed reductions. (a) Reduction of 1,2-diketones. (b) Reduction of imines.

Scheme 36

Hydrogen bonding/HAT/photocatalysed deracemisation of cyclic ureas.

Scheme 37

Hydrogen bonding/HAT/photoredox-catalysed synthesis of cyclic sulfonamides.

Scheme 38

Hydrogen bonding/photoredox-catalysed reaction between imines and indoles.

Scheme 39

Chiral cation/photoredox-catalysed radical coupling of two α-amino radicals.

Scheme 40

Chiral phosphate/photoredox-catalysed hydroetherfication of alkenols.

Scheme 41

Chiral phosphate/photoredox-catalysed synthesis of pyrroloindolines.

Scheme 42

Chiral anion/photoredox-catalysed radical cation Diels–Alder reaction.

Scheme 43

Lewis acid/photoredox-catalysed cycloadditions of carbonyls. (a) Formal [2 + 2] cycloaddition of enones using europium Lewis acid. (b) Formal [3 + 2] cycloaddition of cyclopropyl ketones with styrenes using a gadolinium Lewis acid catalyst.

Scheme 44

Lewis acid/photoredox-catalysed RCA reaction using a scandium Lewis acid between α-amino radicals and α,β-unsaturated amides containing an oxazolidinone auxiliary.

Scheme 45

Lewis acid/photoredox-catalysed RCA reaction using a copper Lewis acid between α-amino radicals and α,β-unsaturated amides containing an azaindoline auxiliary.

Scheme 46

Lewis acid/photoredox-catalysed synthesis of 1,2-amino alcohols from aldehydes and nitrones using a scandium Lewis acid.

Scheme 47

Lewis acid/photocatalysed [2 + 2] photocycloadditions of enones and alkenes.

Scheme 48

Meggers’s chiral-at-metal catalysts.

Scheme 49

Lewis acid/photoredox-catalysed α-functionalisation of ketones with alkyl bromides bearing electron-withdrawing groups. (a) Using bifunctional Lewis acid/photoredox catalyst. (b) Using a dual catalytic system.

Scheme 50

Bifunctional Lewis acid/photoredox-catalysed radical coupling reaction using α-chloroketones and α-aminocarboxylic acids.

Scheme 51

Lewis acid/photocatalysed RCA of enones. (a) Using aldehydes as acyl radical precursors. (b) Other substrates used as radical precursors.

Scheme 52

Bifunctional Lewis acid/photocatalysis for a photocycloaddition of enones.

Scheme 53

Lewis acid/photoredox-catalysed RCA reactions of enones using DHPs as radical precursors.

Scheme 54

Lewis acid/photoredox-catalysed functionalisation of β-ketoesters. (a) Hydroxylation reaction catalysed by a bifunctional nickel/thioxanthone catalyst. (b) Alkylation reaction catalysed by a nickel/iridium dual catalysis system.

Scheme 55

Bifunctional copper-photocatalysed alkylation of imines.

Scheme 56

Copper/photocatalysed alkylation of imines. (a) Bifunctional copper catalysis using α-silyl amines. (b) Dual copper/HAT-catalysed C–H activation of alkanes.

Scheme 57

Bifunctional Lewis acid/photocatalysed intramolecular [2 + 2] photocycloaddition.

Scheme 58

Bifunctional Lewis acid/photocatalysed [2 + 2] photocycloadditions (a) Intramolecular cycloaddition of quinolones. (b) Intermolecular cycloaddition of cyclic enones with terminal alkenes. (c) Intermolecular cycloaddition of phenanthrene-derived aldehydes and tetrasubstituted alkenes.

Scheme 59

Bifunctional Lewis acid/photocatalysed rearrangement of 2,4-dieneones.

Scheme 60

Lewis acid/photocatalysed [2 + 2] cycloadditions of cinnamate esters and styrenes.

Scheme 61

Nickel/photoredox-catalysed arylation of α-amino acids using aryl bromides.

Scheme 62

Nickel/photoredox catalysis. (a) Desymmetrisation of cyclic meso-anhydrides using benzyl trifluoroborate salts. (b) Cross-electrophile coupling of α-chloro esters with aryl iodides, using Hantzsch ester as a sacrificial reductant. (c) C–H Arylation of benzamides with aryl bromides.

Scheme 63

Nickel/photoredox catalysis for the acyl-carbamoylation of alkenes with aldehydes using TBADT as a HAT catalyst.

Scheme 64

Bifunctional copper/photoredox-catalysed C–N coupling between α-chloro amides and carbazoles or indoles.

Scheme 65

Bifunctional copper/photoredox-catalysed difunctionalisation of alkenes with alkynes and alkyl or aryl iodides.

Scheme 66

Copper/photoredox-catalysed decarboxylative cyanation of benzyl phthalimide esters.

Scheme 67

Copper/photoredox-catalysed cyanation reactions using TMSCN. (a) Propargylic cyanation (b) Ring opening cyanation of oxime esters. (c) Radical relay reaction using phthalimide esters and styrenes. (d) Bifunctional catalyst for the difunctionalisation of alkenes using perfluoroalkyl iodides and styrenes.

Scheme 68

Palladium/photoredox-catalysed allylic alkylation reactions. (a) Using alkyl DHPs as radical precursors. (b) Using tertiary amines as radical precursors.

Scheme 69

Manganese/photoredox-catalysed epoxidation of terminal alkenes.

Scheme 70

Chromium/photoredox-catalysed allylation of aldehydes.

Scheme 71

Enzyme/photoredox-catalysed dehalogenation of halolactones.

Scheme 72

Enzyme/photoredox-catalysed dehalogenative cyclisation.

Scheme 73

Enzyme/photoredox-catalysed reduction of cyclic imines.

Scheme 74

Enzyme/photocatalysed enantioselective reduction of electron-deficient alkenes as mixtures of (E)/(Z)-isomers.

Scheme 75

Enzyme/photoredox catalysis. (a) Deacetoxylation of cyclic ketones. (b) Reduction of heteroaromatic alkenes.

Scheme 76

Enzyme/photoredox-catalysed synthesis of indole-3-ones from 2-arylindoles.

Scheme 77

Enzyme/HAT/photoredox catalysis for the DKR of primary amines.

Scheme 78

Bifunctional enzyme/photoredox-catalysed benzylic C–H hydroxylation of trifluoromethylated arenes.