电化学促进的镍催化的α-氰基乙酸酯的α-芳基化反应

doi:10.61558/2993-074X.3435

摘要/Abstract

摘要：

β-氨基酸在医药领域有着广泛的应用。本文利用镍催化的成对电解策略，发展了一种羰基α-芳基化反应，实现了α-芳基-α-氰基乙酸酯的合成。产物可通过简单还原制备α-芳基-β-氨基酸，具有极高的附加价值。在温和条件下，以缺电子芳基溴与α-氰基乙酸酯为底物，可以良好的收率获得目标产物，且具有较好的官能团兼容性。当芳基溴过于富电子时，目标产物发生自偶联。使用DFT计算了产物负离子的还原电势，表明了富电子芳基取代使产物还原电势降低，更易于在阳极发生氧化。通过电化学分析和机理实验，推测为烯醇负离子配体交换型机理而非自由基加成型机理。

关键词: 有机电合成, 镍催化, 成对电解, α-芳基化, DFT计算

Abstract:

β-Amino acids have a wide range of applications in the field of pharmaceuticals. Utilizing a combination strategy of nickel catalysis and paired electrolysis, a catalytic α-arylation protocol of carbonyl compounds has been developed. This protocol affords various α-aryl-α-cyanoacetates, which can be reduced to high-value-added α-aryl-β-amino acids. The cross-coupling reaction of electron-deficient aryl bromides with α-cyanoacetates achieves the expected products with good yields and functional group compatibility under mild conditions. Excessive electron-richness in initial aryl bromides facilitates the self-coupling of desired products. DFT calculations confirm that the presence of electron-rich aryl substitutions decreases the reduction potentials of the product anions, making them more susceptible to oxidation at the anode. Based on electroanalyses and mechanistic studies, it is proposed that the enolate intermediate, rather than the radical intermediate, participates in the catalytic cycle.

Key words: organic electrosynthesis, nickel-catalysis, paired electrolysis, α-arylation, DFT calculation

李子萌, 李章健, 方萍, 梅天胜. 电化学促进的镍催化的α-氰基乙酸酯的α-芳基化反应[J]. 电化学（中英文）, 2024, 30(5): 2313004.

Zi-Meng Li, Zhang-Jian Li, Anat Milo, Ping Fang, Tian-Sheng Mei. Nickel-Catalyzed α-Arylation of α-Cyanoacetates Enabled by Electrochemistry[J]. Journal of Electrochemistry, 2024, 30(5): 2313004.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://electrochem.xmu.edu.cn/CN/10.61558/2993-074X.3435

https://electrochem.xmu.edu.cn/CN/Y2024/V30/I5/2313004

图/表 14

参考文献 38

[1]	Lelais G, Seebach D. β²-amino acids—syntheses, occurrence in natural products, and components of β-peptides[J]. Pept. Sci., 2004, 76(3): 206-243.
[2]	Seebach D, Overhand M, Kühnle F N M, Martinoni B, Oberer L, Hommel U, Widmer H. β-peptides: Synthesis by Arndt-Eistert homologation with concomitant peptide coupling. Structure determination by NMR and CD spectroscopy and by X-ray crystallography. Helical secondary structure of a β-hexapeptide in solution and its stability towards pepsin[J]. Helv. Chim. Acta, 1996, 79(4): 913-941.
[3]	Appella D H, Christianson L A, Karle I L, Powell D R, Gellman S H. β-peptide foldamers: robust helix formation in a new family of β-amino acid oligomers[J]. J. Am. Chem. Soc., 1996, 118(51): 13071-13072.
[4]	Seebach D, Abele S, Schreiber J V, Martinoni B, Nussbaum A K, Schild H, Schulz H, Hennecke H, Woessner R, Bitsch F. Biological and pharmacokinetic studies with β-peptides[J]. Chimia, 1998, 52(12): 734-739.
[5]	Podlech J, Seebach D. The arndt-eistert reaction in peptide chemistry: A facile access to homopeptides[J]. Angew. Chem. Int. Ed., 1995, 34(4): 471-472.
[6]	Semmelhack M F, Stauffer R D, Rogerson T D. Nucleophilic aromatic substitution via a new nickel-catalyzed process and via the S_RN1 reaction. Improved synthesis of cephalotaxinone[J]. Tetrahedron Lett., 1973, 14(45): 4519-4522.
[7]	Semmelhack M F, Chong B P, Stauffer R D, Rogerson T D, Chong A, Jones L D. Total synthesis of the Cephalotaxus alkaloids. Problem in nucleophilic aromatic substitution[J]. J. Am. Chem. Soc., 1975, 97(9): 2507-2516. pmid: 1133420
[8]	Satoh T, Kawamura Y, Miura M, Nomura M. Palladium-catalyzed regioselective mono- and diarylation reactions of 2-phenylphenols and naphthols with aryl halides[J]. Angew. Chem. Int. Ed. Engl., 1997, 36(16): 1740-1742.
[9]	Palucki M, Buchwald S L. Palladium-catalyzed α-arylation of ketones[J]. J. Am. Chem. Soc., 1997, 119(45): 11108-11109.
[10]	Hamann B C, Hartwig J F. Palladium-catalyzed direct α-arylation of ketones. rate acceleration by sterically hindered chelating ligands and reductive elimination from a transition metal enolate complex[J]. J. Am. Chem. Soc., 1997, 119(50): 12382-12383.
[11]	Matsubara K, Ueno K, Koga Y, Hara K. Nickel-NHC-catalyzed α-arylation of acyclic ketones and amination of haloarenes and unexpected preferential N-Arylation of 4-aminopropiophenone[J]. J. Org. Chem., 2007, 72(14): 5069-5076. pmid: 17559270
[12]	Terrett J A, Cuthbertson J D, Shurtleff V W, MacMillan D W C. Switching on elusive organometallic mechanisms with photoredox catalysis[J]. Nature, 2015, 524: 330-334.
[13]	Liu D, Ma H X, Fang P, Mei T S. Nickel-catalyzed thiolation of aryl halides and heteroaryl halides through electrochemistry[J]. Angew. Chem. Int. Ed., 2019, 58(15): 5033-5037. doi: 10.1002/anie.201900956 pmid: 30735304
[14]	Liu D, Liu Z R, Ma C, Jiao K J, Sun B, Wei L, Lefranc J, Herbert S, Mei T S. Nickel-catalyzed N-arylation of NH-sulfoximines with aryl halides via paired electrolysis[J]. Angew. Chem. Int. Ed., 2021, 60(17): 9444-9449.
[15]	Wei L, Wang Z H, Jiao K J, Liu D, Ma C, Fang P, Mei T S. Esterification of carboxylic acids with aryl halides via the merger of paired electrolysis and nickel catalysis[J]. J. Org. Chem., 2021, 86(22): 15906-15913.
[16]	Wang Z H, Wei L, Jiao K J, Ma C, Mei T S. Nickel-catalyzed decarboxylative cross-coupling of indole-3-acetic acids with aryl bromides by convergent paired electrolysis[J]. Chem. Commun., 2022, 58(59): 8202-8205.
[17]	Liu D, Liu Z R, Wang Z H, Ma C, Herbert S, Schirok H, Mei T S. Paired electrolysis-enabled nickel-catalyzed enantioselective reductive cross-coupling between α-chloroesters and aryl bromides[J]. Nat. Commun., 2022, 13: 7318. doi: 10.1038/s41467-022-35073-z pmid: 36443306
[18]	Espinoza E M, Clark J A, Soliman J, Derr J B, Morales M, Vullev V I. Practical aspects of cyclic voltammetry: How to estimate reduction potentials when irreversibility prevails[J]. J. Electrochem. Soc., 2019, 166(5): H3175-H3187. doi: 10.1149/2.0241905jes
[19]	Frisch M J, Trucks G W, Schlegel H B, Scuseria G E, Robb M A, Cheeseman J R, Scalmani G, Barone V, Petersson G A, Nakatsuji H, Li X, Caricato M, Marenich A V, Bloino J, Janesko B G, Gomperts R, Mennucci B, Hratchian H P, Ortiz J V, Izmaylov A F, Sonnenberg J L, Williams-Young D, Ding F, Lipparini F, Egidi F, Goings J, Peng B, Petrone A, Henderson T, Ranasinghe D, Zakrzewski V G, Gao J, Rega N, Zheng G, Liang W, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Throssell K, Montgomery J A, Jr, Peralta J E, Ogliaro F, Bearpark M J, Heyd J J, Brothers E N, Kudin K N, Staroverov V N, Keith T A, Kobayashi R, Normand J, Raghavachari K, Rendell A P, Burant J C, Iyengar S S, Tomasi J, Cossi M, Millam J M, Klene M, Adamo C, Cammi R, Ochterski J W, Martin R L, Morokuma K, Farkas O, Foresman J B, Fox D J. Gaussian 16[CP]. Revision A.03. Wallingford, CT: Gaussian, Inc., 2016.
[20]	Adamo C, Barone V. Toward reliable density functional methods without adjustable parameters: The PBE0 model[J]. J. Chem. Phys., 1999, 110: 6158-6170.
[21]	Grimme S, Antony J, Ehrlich S, Krieg H. A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu[J]. J. Chem. Phys., 2010, 132: 154104.
[22]	Grimme S, Ehrlich S, Goerigk L. Effect of the damping function in dispersion corrected density functional theory[J]. J. Comput. Chem., 2011, 32(7): 1456-1465. doi: 10.1002/jcc.21759 pmid: 21370243
[23]	Marenich A V, Cramer C J, Truhlar D G. Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions[J]. J. Phys. Chem. B, 2009, 113(18): 6378-6396.
[24]	Weigenda F, Ahlrichsb R. Balanced basis sets of split valence, triple zeta valence and quadruple zeta valence quality for H to Rn: Design and assessment of accuracy[J]. Phys. Chem. Chem. Phys., 2005, 7(18): 3297-3305. doi: 10.1039/b508541a pmid: 16240044
[25]	Weigenda F. Accurate coulomb-fitting basis sets for H to Rn[J]. Phys. Chem. Chem. Phys., 2006, 8(9): 1057-1065. doi: 10.1039/b515623h pmid: 16633586
[26]	Legault C Y. CYLView[CP]. 1.0b, Sherbrooke, QC: Université de Sherbrooke, http://www.cylview.org ; 2009.
[27]	Li Y H. Energy diagram plotter CDXML[CP]. 3.5.2, Zenodo, 2023, https://doi.org/10.5281/zenodo.7634466.
[28]	Lu T, Chen F. Multiwfn: A multifunctional wavefunction analyzer[J]. J. Comput. Chem., 2012, 33(5): 580-592. doi: 10.1002/jcc.22885 pmid: 22162017
[29]	Lu T, Chen Q. Independent gradient model based on Hirshfeld partition: A new method for visual study of interactions in chemical systems[J]. J. Comput. Chem., 2022, 43(8): 539-555. doi: 10.1002/jcc.26812 pmid: 35108407
[30]	Humphrey W, Dalke A, Schulten K. VMD: Visual molecular dynamics[J]. J. Molec. Graphics, 1996, 14(1): 33-38.
[31]	Stone J E. An efficient library for parallel ray tracing and animation[D]. Missouri, USA: University of Missouri-Rolla, 1998.
[32]	Oka N, Yamada T, Sajiki H, Akai S, Ikawa T. Aryl boronic esters are stable on silica gel and reactive under Suzuki-Miyaura coupling conditions[J]. Org. Lett., 2022, 24(19): 3510-3514. doi: 10.1021/acs.orglett.2c01174 pmid: 35500272
[33]	Haynes W M, Lide D R, Bruno T J. CRC Handbook of Chemistry and Physics[M]. 97th ed. Boca Raton, USA: CRC Press, 2016. 6-199-6-220.
[34]	Kawamata Y, Vantourout J C, Hickey D P, Bai P, Chen L, Hou Q, Qiao W, Barman K, Edwards M A, Garrido-Castro A F, deGruyter J N, Nakamura H, Knouse K, Qin C, Clay K J, Bao D, Li C, Starr J T, Garcia-Irizarry C, Sach N, White H S, Neurock M, Minteer S D, Baran P S. Electrochemically driven, Ni-catalyzed aryl amination: scope, mechanism, and applications[J]. J. Am. Chem. Soc., 2019, 141(15): 6392-6402. doi: 10.1021/jacs.9b01886 pmid: 30905151
[35]	Till N A, Oh S, MacMillan D W C, Bird M J. The application of pulse radiolysis to the study of Ni(I) intermediates in Ni-catalyzed cross-coupling reactions[J]. J. Am. Chem. Soc., 2021, 143(25): 9332-9337. doi: 10.1021/jacs.1c04652 pmid: 34128676
[36]	Gutierrez O, Tellis J C, Primer D N, Molander G A, Kozlowski M C. Nickel-catalyzed cross-coupling of photoredox-generated radicals: uncovering a general manifold for stereoconvergence in nickel-catalyzed cross-couplings[J]. J. Am. Chem. Soc., 2015, 137(15): 4896-4899. doi: 10.1021/ja513079r pmid: 25836634
[37]	Yakhvarov D G, Samieva E G, Tazeev D I, Budnikovaa Y G. The reactivity of 2,2′-bipyridine complexes in the electrochemical reduction of organohalides[J]. Russ. Chem. Bull., Int. Ed., 2002, 51: 796-804.
[38]	Diccianni J, Lin Q, Diao T. Mechanisms of nickel-catalyzed coupling reactions and applications in alkene functionalization[J]. Acc. Chem. Res., 2020, 53(4): 906-919.