New advances in asymmetric organocatalysis

Editor: Prof. Radovan Šebesta
Comenius University Bratislava

Asymmetric organocatalysis became one of the principal methods for the catalytic synthesis of chiral compounds. This thematic issue in the Beilstein Journal of Organic Chemistry aims to highlight new developments across all subdisciplines of enantioselective organocatalysis. This timely collection of articles deals with methodological advances in both covalent (enamine, iminium, phosphine, carbene, etc.) and noncovalent organocatalytic activations, which are often connected to developments of new catalysts. Important mechanistic and computational studies deepen our understanding of this topic and the underlying processes. The gradual maturation of this field is demonstrated by applications of its methodologies to target molecules synthesis, such as natural products or compounds of medicinal interest.

New advances in asymmetric organocatalysis

Radovan Šebesta

Editorial
Published 28 Feb 2022

PDF

Graphical Abstract

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

Full Text

Chiral isothiourea-catalyzed kinetic resolution of 4-hydroxy[2.2]paracyclophane

David Weinzierl and
Mario Waser

Letter
Published 08 Apr 2021

PDF
Album
1. Graphical Abstract
2. Scheme 1: Overview about established methods to access enantioenriched 2 and the herein investigated kinetic ...
  
  Jump to Scheme 1
3. Scheme 2: Use of alternative acylating agents 4 for the kinetic resolution of rac-2.
  
  Jump to Scheme 2
Supp. Info

Graphical Abstract

Beilstein J. Org. Chem. 2021, 17, 800–804, doi:10.3762/bjoc.17.68

Full Text

Organocatalytic asymmetric Michael/acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones

Chandrakanta Parida and
Subhas Chandra Pan

Full Research Paper
Published 14 Jun 2021

PDF
Album
1. Graphical Abstract
2. Scheme 1: Reactions of α-nitroketones with unsaturated pyrazolone and with 4-benzylidenepyrrolidine-2,3-dione....
  
  Jump to Scheme 1
3. Scheme 2: Reaction of 4-benzylidenedihydrofuran-2,3-dione (4) with α-nitroketones 2b,c. Reaction conditions: ...
  
  Jump to Scheme 2
Supp. Info

Graphical Abstract

Beilstein J. Org. Chem. 2021, 17, 1447–1452, doi:10.3762/bjoc.17.100

Full Text

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

Susanne M. Fischer,
Simon Renner,
A. Daniel Boese and
Christian Slugovc

Full Research Paper
Published 21 Jul 2021

PDF
Album
1. Graphical Abstract
2. Scheme 1: Mechanism for the phosphine-initiated oxa-Michael addition.
  
  Jump to Scheme 1
3. Figure 1: Above: Michael acceptors, Michael donors and catalysts used in this study; pK_a (respectively pK_a of...
  
  Jump to Figure 1
4. Figure 2: Left: double-bond conversion of the polymerization of 4 initiated by 5 mol % TPP, MMTPP or TMTPP af...
  
  Jump to Figure 2
5. Figure 3: Left: Oxidation stability of the phosphines. Phosphine oxide content in % as determined by ³¹P NMR ...
  
  Jump to Figure 3
Supp. Info

Graphical Abstract

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

Full Text

Asymmetric organocatalyzed synthesis of coumarin derivatives

Natália M. Moreira,
Lorena S. R. Martelli and
Arlene G. Corrêa

Review
Published 03 Aug 2021

PDF
Album
1. Graphical Abstract
2. Figure 1: Coumarin-derived commercially available drugs.
  
  Jump to Figure 1
3. Figure 2: Inhibition of acetylcholinesterase by coumarin derivatives.
  
  Jump to Figure 2
4. Scheme 1: Michael addition of 4-hydroxycoumarins 1 to α,β‐unsaturated enones 2.
  
  Jump to Scheme 1
5. Scheme 2: Organocatalytic conjugate addition of 4-hydroxycoumarin 1 to α,β-unsaturated aldehydes 2 followed b...
  
  Jump to Scheme 2
6. Scheme 3: Synthesis of 3,4-dihydrocoumarin derivatives 10 through decarboxylative and dearomatizative cascade...
  
  Jump to Scheme 3
7. Scheme 4: Total synthesis of (+)-smyrindiol (17).
  
  Jump to Scheme 4
8. Scheme 5: Michael addition of 4-hydroxycoumarin (1) to enones 2 through a bifunctional modified binaphthyl or...
  
  Jump to Scheme 5
9. Scheme 6: Michael addition of ketones 20 to 3-aroylcoumarins 19 using a cinchona alkaloid-derived primary ami...
  
  Jump to Scheme 6
10. Scheme 7: Enantioselective reaction of cyclopent-2-enone-derived MBH alcohols 24 with 4-hydroxycoumarins 1.
  
  Jump to Scheme 7
11. Scheme 8: Sequential Michael addition/hydroalkoxylation one-pot approach to annulated coumarins 28 and 30.
  
  Jump to Scheme 8
12. Scheme 9: Michael addition of 4-hydroxycoumarins 1 to enones 2 using a binaphthyl diamine catalyst 31.
  
  Jump to Scheme 9
13. Scheme 10: Asymmetric Michael addition of 4-hydroxycoumarin 1 with α,β-unsaturated ketones 2 catalyzed by a ch...
  
  Jump to Scheme 10
14. Scheme 11: Catalytic asymmetric β-C–H functionalization of ketones via enamine oxidation.
  
  Jump to Scheme 11
15. Scheme 12: Enantioselective synthesis of polycyclic coumarin derivatives 37 catalyzed by an primary amine-imin...
  
  Jump to Scheme 12
16. Scheme 13: Allylic alkylation reaction between 3-cyano-4-methylcoumarins 39 and MBH carbonates 40.
  
  Jump to Scheme 13
17. Scheme 14: Enantioselective synthesis of cyclopropa[c]coumarins 45.
  
  Jump to Scheme 14
18. Scheme 15: NHC-catalyzed lactonization of 2-bromoenals 46 with 4-hydroxycoumarin (1).
  
  Jump to Scheme 15
19. Scheme 16: NHC-catalyzed enantioselective synthesis of dihydrocoumarins 51.
  
  Jump to Scheme 16
20. Scheme 17: Domino reaction of enals 2 with hydroxylated malonate 53 catalyzed by NHC 55.
  
  Jump to Scheme 17
21. Scheme 18: Oxidative [4 + 2] cycloaddition of enals 57 to coumarins 56 catalyzed by NHC 59.
  
  Jump to Scheme 18
22. Scheme 19: Asymmetric [3 + 2] cycloaddition of coumarins 43 to azomethine ylides 60 organocatalyzed by quinidi...
  
  Jump to Scheme 19
23. Scheme 20: Synthesis of α-benzylaminocoumarins 64 through Mannich reaction between 4-hydroxycoumarins (1) and ...
  
  Jump to Scheme 20
24. Scheme 21: Asymmetric addition of malonic acid half-thioesters 67 to coumarins 66 using the sulphonamide organ...
  
  Jump to Scheme 21
25. Scheme 22: Enantioselective 1,4-addition of azadienes 71 to 3-homoacyl coumarins 70.
  
  Jump to Scheme 22
26. Scheme 23: Michael addition/intramolecular cyclization of 3-acylcoumarins 43 to 3-halooxindoles 74.
  
  Jump to Scheme 23
27. Scheme 24: Enantioselective synthesis of 3,4-dihydrocoumarins 78 catalyzed by squaramide 73.
  
  Jump to Scheme 24
28. Scheme 25: Organocatalyzed [4 + 2] cycloaddition between 2,4-dienals 79 and 3-coumarincarboxylates 43.
  
  Jump to Scheme 25
29. Scheme 26: Enantioselective one-pot Michael addition/intramolecular cyclization for the synthesis of spiro[dih...
  
  Jump to Scheme 26
30. Scheme 27: Michael/hemiketalization addition enantioselective of hydroxycoumarins (1) to: (a) enones 2 and (b)...
  
  Jump to Scheme 27
31. Scheme 28: Synthesis of 2,3-dihydrofurocoumarins 89 through Michael addition of 4-hydroxycoumarins 1 to β-nitr...
  
  Jump to Scheme 28
32. Scheme 29: Synthesis of pyrano[3,2-c]chromene derivatives 93 via domino reaction between 4-hydroxycoumarins (1...
  
  Jump to Scheme 29
33. Scheme 30: Conjugated addition of 4-hydroxycoumarins 1 to nitroolefins 95.
  
  Jump to Scheme 30
34. Scheme 31: Michael addition of 4-hydroxycoumarin 1 to α,β-unsaturated ketones 2 promoted by primary amine thio...
  
  Jump to Scheme 31
35. Scheme 32: Enantioselective synthesis of functionalized pyranocoumarins 99.
  
  Jump to Scheme 32
36. Scheme 33: 3-Homoacylcoumarin 70 as 1,3-dipole for enantioselective concerted [3 + 2] cycloaddition.
  
  Jump to Scheme 33
37. Scheme 34: Synthesis of warfarin derivatives 107 through addition of 4-hydroxycoumarins 1 to β,γ-unsaturated α...
  
  Jump to Scheme 34
38. Scheme 35: Asymmetric multicatalytic reaction sequence of 2-hydroxycinnamaldehydes 109 with 4-hydroxycoumarins ...
  
  Jump to Scheme 35
39. Scheme 36: Mannich asymmetric addition of cyanocoumarins 39 to isatin imines 112 catalyzed by the amide-phosph...
  
  Jump to Scheme 36
40. Scheme 37: Enantioselective total synthesis of (+)-scuteflorin A (119).
  
  Jump to Scheme 37

Graphical Abstract

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

Full Text

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

Zara M. Seibel,
Jeffrey S. Bandar and
Tristan H. Lambert

Letter
Published 17 Aug 2021

PDF
Album
1. Graphical Abstract
2. Figure 1: Strategy for the synthesis of glutamate and pyroglutamate derivatives and several natural products ...
  
  Jump to Figure 1
3. Figure 2: Effect of the aryl substituent on reaction efficiency and selectivity.
  
  Jump to Figure 2
4. Figure 3: Proposed transition state model.
  
  Jump to Figure 3
Supp. Info

Graphical Abstract

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

Full Text

Halides as versatile anions in asymmetric anion-binding organocatalysis

Lukas Schifferer,
Martin Stinglhamer,
Kirandeep Kaur and
Olga García Macheño

Review
Published 01 Sep 2021

PDF
Album
1. Graphical Abstract
2. Figure 1: a) Binding interactions in the chloride channel of E. coli. and b) examples of chloride, cyanide, n...
  
  Jump to Figure 1
3. Figure 2: a) H-bond vs anion-binding catalysis and b) activation modes in anion-binding catalysis.
  
  Jump to Figure 2
4. Scheme 1: First proposed anion-binding mechanism in the thiourea-catalyzed acetalization of benzaldehyde.
  
  Jump to Scheme 1
5. Scheme 2: a) Thiourea-catalyzed enantioselective acyl-Pictet–Spengler reaction of tryptamine-derived imines 4...
  
  Jump to Scheme 2
6. Scheme 3: Proposed mechanism of the thiourea-catalyzed enantioselective Pictet–Spengler reaction of hydroxyla...
  
  Jump to Scheme 3
7. Scheme 4: a) Thiourea-catalyzed intramolecular Pictet–Spengler-type cyclization of hydroxylactam-derived N-ac...
  
  Jump to Scheme 4
8. Scheme 5: Enantioselective Reissert-type reactions of a) (iso)quinolines with silyl ketene acetals, and b) vi...
  
  Jump to Scheme 5
9. Figure 3: Role of the counter-anion: a) Anion acting as a spectator and b) anion participating directly as th...
  
  Jump to Figure 3
10. Scheme 6: Enantioselective selenocyclization catalyzed by squaramide 28.
  
  Jump to Scheme 6
11. Scheme 7: Desymmetrization of meso-aziridines catalyzed by bifunctional thiourea catalyst 31.
  
  Jump to Scheme 7
12. Scheme 8: Anion-binding-catalyzed desymmetrization of a) meso-aziridines catalyzed by chiral triazolium catal...
  
  Jump to Scheme 8
13. Scheme 9: Bis-urea-catalyzed enantioselective fluorination of a) β-bromosulfides and b) β-haloamines by Gouve...
  
  Jump to Scheme 9
14. Scheme 10: a) Bifunctional thiourea anion-binding – basic/nucleophilic catalysts. Selected applications in b) ...
  
  Jump to Scheme 10
15. Scheme 11: Thiourea-catalyzed enantioselective polycyclization reaction of hydroxylactams 51 through cation–π ...
  
  Jump to Scheme 11
16. Scheme 12: Enantioselective aza-Sakurai cyclization of hydroxylactams 56 implicating additional cation–π and L...
  
  Jump to Scheme 12
17. Scheme 13: Enantioselective tail-to-head cyclization of neryl chloride derivatives.
  
  Jump to Scheme 13
18. Scheme 14: Cation–π interactions in anion binding-catalyzed asymmetric addition reactions: a) addition of indo...
  
  Jump to Scheme 14
19. Scheme 15: Bisthiourea catalyzed oxa-Pictet–Spengler reaction of indole-based alcohols and aromatic aldehydes ...
  
  Jump to Scheme 15
20. Scheme 16: Anion-binding catalyst development in the enantioselective addition of silyl ketene acetals to 1-ch...
  
  Jump to Scheme 16
21. Scheme 17: a) Macrocyclic bis-thiourea catalyst in a diastereoselective glycosylation reaction. b) Competing S_N...
  
  Jump to Scheme 17
22. Scheme 18: a) Folding mechanism of oligotriazoles upon anion recognition. b) Representative tetratriazole 82 c...
  
  Jump to Scheme 18
23. Scheme 19: Switchable chiral tetratriazole catalyst 86 in the enantioselective addition of silyl ketene acetal...
  
  Jump to Scheme 19

Graphical Abstract

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

Full Text

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

Mili Litvajova,
Emiliano Sorrentino,
Brendan Twamley and
Stephen J. Connon

Letter
Published 02 Sep 2021

PDF
Album
1. Graphical Abstract
2. Figure 1: The importance of the 3,3-spirooxindole core and its access through enantioselective enolate alkyla...
  
  Jump to Figure 1
3. Scheme 1: A) S_N2 alkylation of 3-subtituted-2-oxindoles not readily functionalisable; B) Previous work: enant...
  
  Jump to Scheme 1
4. Figure 2: Substrate scope. ^aIsolated yield. ^bDetermined by CSP-HPLC. ^cValue in brackets refers to reaction co...
  
  Jump to Figure 2
5. Scheme 2: Enantioselective synthesis of a CRTH2 receptor antagonist.
  
  Jump to Scheme 2
Supp. Info

Graphical Abstract

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

Full Text

Enantioselective PCCP Brønsted acid-catalyzed aminalization of aldehydes

Martin Kamlar,
Robert Reiberger,
Martin Nigríni,
Ivana Císařová and
Jan Veselý

Full Research Paper
Published 16 Sep 2021

PDF
Album
1. Graphical Abstract
2. Figure 1: Synthetic strategies employing chiral Brønsted acid catalysis.
  
  Jump to Figure 1
3. Scheme 1: The substrate scope of the aminalization reaction for different aldehydes. ^aAfter recrystallization...
  
  Jump to Scheme 1
4. Scheme 2: The substrate scope of the intermolecular aminalization reaction for anthranilamide derivatives. ^aA...
  
  Jump to Scheme 2
5. Figure 2: X-ray single-crystal structure of aminal 3l with the displacement ellipsoids drawn at the 30% proba...
  
  Jump to Figure 2
Supp. Info

Graphical Abstract

Beilstein J. Org. Chem. 2021, 17, 2433–2440, doi:10.3762/bjoc.17.160

Full Text

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

Pratibha Sharma,
Raakhi Gupta and
Raj K. Bansal

Review
Published 18 Oct 2021

PDF
Album
1. Graphical Abstract
2. Scheme 1: Asymmetric aza-Michael addition catalyzed by cinchona alkaloid derivatives.
  
  Jump to Scheme 1
3. Scheme 2: Intramolecular 6-exo-trig aza-Michael addition reaction.
  
  Jump to Scheme 2
4. Scheme 3: Asymmetric aza-Michael/Michael addition cascade reaction of 2-nitrobenzofurans and 2-nitrobenzothio...
  
  Jump to Scheme 3
5. Scheme 4: Asymmetric aza-Michael addition of para-dienone imide to benzylamine.
  
  Jump to Scheme 4
6. Scheme 5: Asymmetric synthesis of chiral N-functionalized heteroarenes.
  
  Jump to Scheme 5

Graphical Abstract

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

Full Text

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

Viera Poláčková,
Dominika Krištofíková,
Boglárka Némethová,
Renata Górová,
Mária Mečiarová and
Radovan Šebesta

Full Research Paper
Published 25 Oct 2021

PDF
Album
1. Graphical Abstract
2. Figure 1: Catalyst design principles.
  
  Jump to Figure 1
3. Scheme 1: Synthesis of isothiocyanate 3a and isocyanate 3b.
  
  Jump to Scheme 1
4. Scheme 2: Synthesis of sulfinylthioureas C1 and ureas C2.
  
  Jump to Scheme 2
5. Scheme 3: Synthesis of adducts 8a,d,f in solution.
  
  Jump to Scheme 3
6. Figure 2: DFT-calculated (PBEh-3c/def2-SV(P)//M06-2X/def2-TZVP) structures of catalyst (S,R) and (S,S)-C2, en...
  
  Jump to Figure 2
7. Figure 3: a) Arrangements of reactants in the transition states; b) DFT-calculated (PBEh-3c/def2-SV(P)//M06-2...
  
  Jump to Figure 3
8. Figure 4: DFT-calculated (PBEh-3c/def2-SV(P)//M06-2X/def2-TZVP) reaction profile for the Michael addition of ...
  
  Jump to Figure 4
Supp. Info

Graphical Abstract

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

Full Text

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

Akhil K. Dubey and
Raghunath Chowdhury

Full Research Paper
Published 27 Oct 2021

PDF
Album
1. Graphical Abstract
2. Scheme 1: Selected methods for the synthesis of enantioenriched β-silyl nitroalkanes, synthesis of chiral org...
  
  Jump to Scheme 1
3. Scheme 2: Scope of substrates. Reaction conditions: 1 (0.2 mmol), 2 (0.5 mmol), catalyst VII (0.01 mmol, 5 mo...
  
  Jump to Scheme 2
4. Scheme 3: Synthesis of ent-3. Reaction conditions: 1 (0.2 mmol), 2 (0.5 mmol), catalyst VIII (0.01 mmol, 5 mo...
  
  Jump to Scheme 3
5. Scheme 4: Organocatalytic 1,4-conjuagte addition of nitromethane (2) to enone 3o.
  
  Jump to Scheme 4
6. Figure 1: Single crystal X-ray structure of ent-3k (CCDC 2097263).
  
  Jump to Figure 1
7. Scheme 5: Preparative scale synthesis of 3c and ent-3d.
  
  Jump to Scheme 5
Supp. Info

Graphical Abstract

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

Full Text

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

Jiang-Song Zhai and
Da-Ming Du

Full Research Paper
Published 04 Jan 2022

PDF
Album
1. Graphical Abstract
2. Figure 1: Selected examples of natural products and drugs possessing the indane scaffold.
  
  Jump to Figure 1
3. Scheme 1: Known strategies and conceptual advance of this contribution.
  
  Jump to Scheme 1
4. Figure 2: Selected examples of bioactive spirobarbiturates.
  
  Jump to Figure 2
5. Figure 3: The screened organocatalysts.
  
  Jump to Figure 3
6. Scheme 2: Substrate scope of 2-isothiocyanato-1-indanones. The reactions were carried out with 1 (0.12 mmol), ...
  
  Jump to Scheme 2
7. Scheme 3: Substrate scope of barbiturate-based olefins. The reactions were carried out with 1a (0.12 mmol), 2...
  
  Jump to Scheme 3
8. Figure 4: X-ray crystal structure of 3ae (displacement ellipsoids are drawn at the 50% probability level).
  
  Jump to Figure 4
9. Scheme 4: Gram-scale synthesis of 3ah.
  
  Jump to Scheme 4
10. Scheme 5: Further transformation of 3ah.
  
  Jump to Scheme 5
11. Scheme 6: One-pot three-component reaction.
  
  Jump to Scheme 6
12. Scheme 7: Proposed reaction mechanism.
  
  Jump to Scheme 7
Supp. Info

Graphical Abstract

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

Full Text

Back to all Issues

Other Beilstein-Institut Open Science Activities

Keep Informed

RSS Feed

Subscribe to our Latest Articles RSS Feed.

Subscribe

Email Notification

Register and get informed about new articles.

Register

Follow the Beilstein-Institut

Twitter: @BeilsteinInst