Organocatalytic Conjugate Hydroazidation and Hydrocyanation: A Metal-Free Approach to Synthetically Versatile Chiral Building Blocks
Abstract
1. Introduction
2. Enantioselective Conjugate Azidation
2.1. Organocatalyzed Enantioselective Hydroazidation
2.2. Organocatalyzed Enantioselective Hydrocyanation
3. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
- MacMillan, D.W.C. The advent and development of organocatalysis. Nature 2008, 455, 304–308. [Google Scholar] [CrossRef]
- Albrecht, Ł.; Albrecht, A.; Dell’Amico, L. Asymmetric Organocatalysis: New Strategies, Catalysts, and Opportunities; WILEY-VCH GmbH: Weinheim, Germany, 2023. [Google Scholar]
- Benaglia, M. Organocatalysis—Stereoselective Reactions and Applications in Organic Synthesis; De Gruyter: Berlin, Germany, 2021. [Google Scholar]
- García Mancheño, O.; Waser, M. Recent Developments and Trends in Asymmetric Organocatalysis. Eur. J. Org. Chem. 2023, 26, e202200950. [Google Scholar] [CrossRef]
- Vogel, P.; Lam, Y.-H.; Simon, A.; Kouk, K.N. Organocatalysis: Fundamentals and Comparisons to Metal and Enzyme Catalysis. Catalysts 2016, 6, 128. [Google Scholar] [CrossRef]
- Brase, S.; Gil, C.; Knepper, K.; Zimmermann, V. Organic Azides: An Exploding Diversity of a Unique Class of Compounds. Angew. Chem. Int. Ed. 2005, 44, 5188–5240. [Google Scholar] [CrossRef]
- Jafarzadeh, M. Trimethylsilyl Azide (TMSN3): A Versatile Reagent in Organic Synthesis. Synlett 2007, 13, 2144–2145. [Google Scholar] [CrossRef]
- Waser, J.; Carreira, E.M. Organic Azides: Syntheses and Applications; Brase, S., Banert, K., Eds.; Wiley-VCH: Weinheim, Germany, 2010; pp. 95–111. [Google Scholar]
- Chiba, S. Application of Organic Azides for the Synthesis of Nitrogen-Containing Molecules. Synlett 2012, 1, 21–44. [Google Scholar] [CrossRef]
- Sivaguru, P.; Ning, Y.; Bi, X. New Strategies for the Synthesis of Aliphatic Azides. Chem. Rev. 2021, 121, 4253–4307. [Google Scholar] [CrossRef] [PubMed]
- Ding, P.-G.; Hu, X.-S.; Zhou, F.; Zhou, J. Catalytic enantioselective synthesis of α-chiral azides. Org. Chem. Front. 2018, 5, 1542–1559. [Google Scholar] [CrossRef]
- Myers, J.K.; Jacobsen, E.N. Asymmetric Synthesis of α-Amino Acid Derivatives via Catalytic Conjugate Addition of Hydrazoic Acid to Unsaturated Imides. J. Am. Chem. Soc. 1999, 121, 8959–8960. [Google Scholar] [CrossRef]
- Taylor, M.S.; Zalatan, D.N.; Lerchner, A.M.; Jacobsen, E.N. Highly Enantioselective Conjugate Additions to α,β-Unsaturated Ketones Catalyzed by a (Salen)Al Complex. J. Am. Chem. Soc. 2005, 127, 1313–1317. [Google Scholar] [CrossRef]
- Guerin, D.J.; Horstmann, T.E.; Miller, S.J. Amine-catalyzed addition of azide ion to α,β-unsaturated carbonyl compounds. Org. Lett. 1999, 1, 1107–1109. [Google Scholar] [CrossRef] [PubMed]
- Horstmann, T.E.; Guerin, D.J.; Miller, S.J. Asymmetric Conjugate Addition of Azide to α,β-Unsaturated Carbonyl Compounds Catalyzed by Simple Peptides. Angew. Chem. Int. Ed. 2000, 39, 3635–3638. [Google Scholar]
- Guerin, D.J.; Miller, S.J. Asymmetric Azidation−Cycloaddition with Open-Chain Peptide-Based Catalysts. A Sequential Enantioselective Route to Triazoles. J. Am. Chem. Soc. 2002, 124, 2134–2136. [Google Scholar] [PubMed]
- Nielsen, M.; Zhuang, W.; Jørgensen, K.A. Asymmetric Conjugate Addition of Azide to α,β-Unsaturated Nitro Compounds Catalyzed by Cinchona Alkaloids. Tetrahedron 2007, 63, 5849–5854. [Google Scholar] [CrossRef]
- Bellavista, T.; Meninno, S.; Lattanzi, A.; Della Sala, G. Asymmetric Hydroazidation of Nitroalkenes Promoted by a Secondary Amine-Thiourea Catalyst. Adv. Synth. Catal. 2015, 357, 3365–3373. [Google Scholar] [CrossRef]
- Shyam, P.K.; Jang, H.-Y. Metal–Organocatalytic Tandem Azide Addition/Oxyamination of Aldehydes for the Enantioselective Synthesis of β-Amino α-Hydroxy Esters. Eur. J. Org. Chem. 2014, 1817–1822. [Google Scholar] [CrossRef]
- Stöckel-Maschek, A.; Stiebitz, B.; Koelschb, R.; Neubert, K. Novel 3-amino-2-hydroxy acids containing protease inhibitors. Part 1: Synthesis and kinetic characterization as aminopeptidase P inhibitors. Bioorg. Med. Chem. 2005, 13, 4806–4818. [Google Scholar] [CrossRef] [PubMed]
- Sato, S.; Tetsuhashi, M.; Sekine, K.; Miyachi, H.; Naito, M.; Hashimoto, Y.; Aoyama, H. Degradation-promoters of cellular inhibitor of apoptosis protein 1 based on bestatin and actinonin. Bioorg. Med. Chem. 2008, 16, 4685–4698. [Google Scholar] [CrossRef]
- Ekegren, J.K.; Unge, T.; Safa, M.Z.; Wallberg, H.; Samuelsson, B.; Hallberg, A. A new class of HIV-1 protease inhibitors containing a tertiary alcohol in the transition-state mimicking scaffold. J. Med. Chem. 2005, 48, 8098–8102. [Google Scholar] [CrossRef]
- Xue, Z.-K.; Fu, N.-K.; Luo, S.-Z. Asymmetric hydroazidation of α-substituted vinyl ketones catalyzed by chiral primary amine. Chin. Chem. Lett. 2017, 28, 1083–1086. [Google Scholar] [CrossRef]
- Humbrías-Martín, J.; Pérez-Aguilar, M.C.; Mas-Ballesté, R.; Dentoni Litta, A.; Lattanzi, A.; Della Sala, G.; Fernández-Salas, G.A.; Alemán, J. Enantioselective Conjugate Azidation of α,β-Unsaturated Ketones under Bifunctional Organocatalysis by Direct Activation of TMSN3. Adv. Synth. Catal. 2019, 361, 4790–4796. [Google Scholar] [CrossRef]
- Jacobsen, E.N.; Mazet, C. Dinuclear {(salen)Al} Complexes Display Expanded Scope in the Conjugate Cyanation of α,β-Unsaturated Imides. Angew. Chem. Int. Ed. 2008, 47, 1762–1765. [Google Scholar]
- Sammis, G.M.; Danjo, H.; Jacobsen, E.N. Cooperative dual catalysis: Application to the highly enantioselective conjugate cyanation of unsaturated imides. J. Am. Chem. Soc. 2004, 125, 9928–9929. [Google Scholar] [CrossRef]
- Sammis, G.M.; Jacobsen, E.N. Highly Enantioselective, Catalytic Conjugate Addition of Cyanide to α,β-Unsaturated Imides. J. Am. Chem. Soc. 2003, 125, 4442–4443. [Google Scholar] [CrossRef]
- Mita, T.; Sasaki, K.; Kanai, M.; Shibasaki, M.J. Catalytic Enantioselective Conjugate Addition of Cyanide to α,β-Unsaturated N-Acylpyrroles. Am. Chem. Soc. 2005, 127, 514–515. [Google Scholar] [CrossRef]
- Bernal, P.; Fernández, R.; Lassaletta, J.M. Organocatalytic Asymmetric Cyanosilylation of Nitroalkenes. Chem. Eur. J. 2010, 16, 7714–7718. [Google Scholar] [CrossRef]
- Bernardi, L.; Fini, F.; Fochi, M.; Ricci, A. Organocatalyzed Enantioselective Synthesis of Nitroalkanes Bearing All-Carbon Quaternary Stereogenic Centers through Conjugate Addition of Acetone Cyanohydrin. Synlett 2008, 12, 1857–1861. [Google Scholar] [CrossRef]
- Provencher, B.A.; Bartelson, K.J.; Liu, Y.; Foxman, B.M.; Deng, L. Structural Study-Guided Development of Versatile Phase-Transfer Catalysts for Asymmetric Conjugate Additions of Cyanide. Angew. Chem. Int. Ed. 2011, 50, 10565–10569. [Google Scholar] [CrossRef]
- Yang, Y.; Wu, S.; Chen, F.-X. Chiral Sodium Phosphate Catalyzed Enantioselective 1,4-Addition of TMSCN to Aromatic Enones. Synlett 2010, 18, 2725–2728. [Google Scholar] [CrossRef]
- Wang, Y.-F.; Zeng, W.; Sohail, M.; Guo, J.; Wu, S.; Chen, F.-X. Highly Efficient Asymmetric Conjugate Hydrocyanation of Aromatic Enones by an Anionic Chiral Phosphate Catalyst. Eur. J. Org. Chem. 2013, 2013, 4624–4633. [Google Scholar] [CrossRef]
Entry | R | t (h) | Yield (%) | ee (%) |
1 | PhCH2CH2 (8a) | 17 | 95 (10a) | 79 |
2 | (CH3)2CH (8b) | 18 | 63 (10b) | 71 |
3 | (CH3)2CHCH2 (8c) | 19 | 78 (10c) | 71 |
4 | CH3(CH2)4 (8d) | 18 | 92 (10d) | 71 |
5 | (CH3)3C (8e) | 15 | 86 (10e) | 82 |
6 | Cyclohexyl (8f) | 15 | 76 (10f) | 75 |
7 | Ph (8g) | 24 | 81 (10g) | 39 |
Entry | R’ | R | Product | Time (h) | Yield (%) | ee (%) |
1 | H | Me | 18a | 16 | 72 | 69 |
2 | 4-F | Me | 18b | 16 | 76 | 70 |
3 | 4-Cl | Me | 18c | 16 | 78 | 70 |
4 | 4-Br | Me | 18d | 16 | 91 | 75 |
5 | 4-OMe | Me | 18e | 18 | 78 | 69 |
6 | 4-CF3 | Me | 18f | 24 | 67 | 59 |
7 | 4-Et | Me | 18g | 16 | 90 | 45 |
8 | 3-F | Me | 18h | 18 | 72 | 44 |
9 | 3-Cl | Me | 18i | 18 | 74 | 55 |
10 | 3-Br | Me | 18j | 18 | 76 | 54 |
11 | 3-OMe | Me | 18k | 24 | 79 | 38 |
12 | 3-Br,4-F | Me | 18l | 24 | 69 | 56 |
13 | H | Et | 18m | 18 | 68 | 43 |
14 | H | n-Pr | 18n | 24 | 68 | 11 |
15 | H | Br | 18o | 32 | 56 | 16 |
Entry | R | R’ | Product | Yield (%) | ee (%) |
1 | Ph | Me | 25a | 72 | 67 |
2 | Ph | Pr | 25b | 60 | 33 |
3 | 2-naphtyl | Me | 25c | 68 | 72 |
4 | 4-ClC6H4 | Me | 25d | 75 | 64 |
5 | 4-MeC6H4 | Me | 25e | 62 | 58 |
6 | 4-MeOC6H4 | Me | 25f | 64 | 56 |
7 | 2-furyl | Me | 25g | 52 | 65 |
Entry | R | R’ | PTC | Product | Time (h) | Yield (%) | ee (%) |
---|---|---|---|---|---|---|---|
1 | Ph | Et | 28 | 30a | 24 | 77 | 95 (S) |
2 | Ph | Et | 29 | 30a | 24 | 97 | 90 (R) |
3 | Ph | Me | 28 | 30b | 24 | 78 | 97(S) |
4 | Ph | Me | 29 | 30b | 24 | 92 | 91(R) |
5 | Ph | n-C5H11 | 28 | 30c | 96 | 89 | 96(S) |
6 | Ph | n-C5H11 | 29 | 30c | 24 | 73 | 92(R) |
7 | Ph | iPr | 28 | 30d | 72 | 69 | 94(S) |
8 | Ph | iPr | 29 | 30d | 24 | 80 | 93(R) |
9 | Ph | CH2iPr | 28 | 30e | 72 | 80 | 97(S) |
10 | Ph | CH2iPr | 29 | 30e | 24 | 91 | 93(R) |
11 | Ph | CH2OSiEt3 | 28 | 30f | 48 | 75 | 93(S) |
12 | Ph | CH2OSiEt3 | 29 | 30f | 24 | 77 | 87(R) |
13 | 4-Me-C6H4 | Me | 28 | 30g | 48 | 78 | 95(S) |
14 | 4-Me-C6H4 | Me | 29 | 30g | 24 | 99 | 92(R) |
15 | 4-OMe-C6H4 | Me | 28 | 30h | 48 | 88 | 97(S) |
16 | 4-OMe-C6H4 | Me | 29 | 30h | 24 | 98 | 94(R) |
17 | 4-Cl-C6H4 | Me | 28 | 30i | 6 | 82 | 96(S) |
18 | 4-Cl-C6H4 | Me | 29 | 30i | 4 | 77 | 90(R) |
Entry | R | R’ | Product | Yield (%) | ee (%) |
---|---|---|---|---|---|
1 | Ph | Ph | 30j | 91 | 95 |
2 | Ph | Ph | 30j | 91 | 94 |
3 | Ph | 4-FC6H4 | 30k | 95 | 96 |
4 | Ph | 4-ClC6H4 | 30l | 93 | 96 |
5 | Ph | 4-BrC6H4 | 30m | 93 | 94 |
6 | 4-MeC6H4 | 3-BrC6H4 | 30n | 96 | 95 |
7 | Ph | 4-MeOC6H4 | 30o | 94 | 97 |
8 | Ph | 4-MeC6H4 | 30p | 93 | 94 |
9 | 4-MeC6H4 | Ph | 30q | 94 | 97 |
10 | 2-MeOC6H4 | Ph | 30r | 72 | 96 |
11 | 3-MeOC6H4 | Ph | 30s | 90 | 92 |
12 | 4-FC6H4 | Ph | 30t | 90 | 98 |
13 | 4-FC6H4 | Ph | 30u | 91 | 93 |
14 | 3-FC6H4 | Ph | 30v | 95 | 96 |
15 | 2-ClC6H4 | Ph | 30n | 93 | 93 |
16 | 4-ClC6H4 | Ph | 30w | 93 | 95 |
17 | 2,4-Cl2C6H3 | Ph | 30x | 96 | 92 |
18 | 4-BrC6H4 | Ph | 30y | 93 | 94 |
19 | tBu | Ph | 30z | 91 | 94 |
18 | cHex | Ph | 30z’ | 91 | 95 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Schettini, R.; Della Sala, G. Organocatalytic Conjugate Hydroazidation and Hydrocyanation: A Metal-Free Approach to Synthetically Versatile Chiral Building Blocks. Symmetry 2024, 16, 199. https://doi.org/10.3390/sym16020199
Schettini R, Della Sala G. Organocatalytic Conjugate Hydroazidation and Hydrocyanation: A Metal-Free Approach to Synthetically Versatile Chiral Building Blocks. Symmetry. 2024; 16(2):199. https://doi.org/10.3390/sym16020199
Chicago/Turabian StyleSchettini, Rosaria, and Giorgio Della Sala. 2024. "Organocatalytic Conjugate Hydroazidation and Hydrocyanation: A Metal-Free Approach to Synthetically Versatile Chiral Building Blocks" Symmetry 16, no. 2: 199. https://doi.org/10.3390/sym16020199
APA StyleSchettini, R., & Della Sala, G. (2024). Organocatalytic Conjugate Hydroazidation and Hydrocyanation: A Metal-Free Approach to Synthetically Versatile Chiral Building Blocks. Symmetry, 16(2), 199. https://doi.org/10.3390/sym16020199