Intensified Continuous Flow Michaelis-Arbuzov Rearrangement toward Alkyl Phosphonates

alkyl phosphonates; continuous flow processes; in-line NMR monitoring; intensification; Michaelis−Arbuzov; α-aminophosphonic acids; Alkyl phosphonate; Competitive reactions; Continuous-flow; Phosphonates; Physical and Theoretical Chemistry; Organic Chemistry

Abstract :

[en] Herein is described the development of an intensified continuous flow process for the preparation of a library of alkyl phosphonates through a Michaelis-Arbuzov rearrangement. A careful process optimization and thorough analysis of the competitive reactions led to a very attractive protocol with unprecedented productivities (up to 4.97 kg of material per day) and a low environmental footprint with the absence of solvent, additives, catalysts, and waste. In-line low-field 31P NMR monitoring was conveniently implemented for rapid optimization and process monitoring. Two key alkyl phosphonate intermediates were also assessed for the unprecedented diazene dicarboxylate-mediated electrophilic amination under continuous flow conditions toward the α-aminophosphonic acid derivatives of Pphenylalanine and Palanine, bioisosters of the natural amino acids phenylalanine and alanine, respectively.

Disciplines :

Chemistry

Author, co-author :

Toupy, Thomas ; Université de Liège - ULiège > Molecular Systems (MolSys)

Monbaliu, Jean-Christophe ; Université de Liège - ULiège > Département de chimie (sciences) > Center for Integrated Technology and Organic Synthesis

Language :

English

Title :

Intensified Continuous Flow Michaelis-Arbuzov Rearrangement toward Alkyl Phosphonates

Publication date :

08 February 2022

Journal title :

Organic Process Research and Development

ISSN :

1083-6160

eISSN :

1520-586X

Publisher :

American Chemical Society

Volume :

Issue :

Pages :

467 - 478

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://pubs.acs.org/doi/pdf/10.1021/acs.oprd.1c00472

Funders :

F.R.S.-FNRS - Fonds de la Recherche Scientifique
FRIA - Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture

Funding text :

This work was supported by the F.R.I.A.-FNRS (Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture, Belgium) and the University of Liège (Welcome Grant WG-13/03, JCMM). T.T. is a F.R.I.A.-FNRS PhD student fellow.

Available on ORBi :

since 07 March 2022

Statistics

Number of views

97 (2 by ULiège)

Number of downloads

2 (2 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

Keglevich, G. Organophosphorus Chemistry 2018. In Molecules; MDPI, 2020, 10.1515/9783110535839.
Amira, A.; Aouf, Z.; K’tir, H.; Chemam, Y.; Ghodbane, R.; Zerrouki, R.; Aouf, N. Recent Advances in the Synthesis of α-Aminophosphonates: A Review. ChemistrySelect 2021, 6, 6137- 6149, 10.1002/slct.202101360
Monbaliu, J.-C.; Tinant, B.; Marchand-Brynaert, J. [4 + 2] Cycloadditions of 1-Phosphono-1,3-Butadienes with Nitroso Heterodienophiles: A Versatile Synthetic Route for Polyfunctionalized Aminophosphonic Derivatives. J. Org. Chem. 2010, 75, 5478- 5486, 10.1021/jo100230r
Monbaliu, J.-C.; Tinant, B.; Peeters, D.; Marchand-Brynaert, J. Novel Chiral 1-Phosphono-1,3-Butadiene for Asymmetric Hetero Diels-Alder Cycloadditions with Nitroso and Azodicarboxylate Dienophiles. Tetrahedron Lett. 2010, 51, 1052- 1055, 10.1016/j.tetlet.2009.12.063
Engel, R. Handbook of Organophosphorus Chemistry; Engel, R., Ed., CRC Press: New York, US, 1992.
Purohit, A. K.; Kumar, A.; Singh, V.; Goud, D. R.; Jain, R.; Dubey, D. K. Polymer-Supported Sulfonated Magnetic Resin: An Efficient Reagent for Esterification of O-Alkyl Alkylphosphonic-and Carboxylic-Acids. Tetrahedron Lett. 2014, 55, 6844- 6846, 10.1016/j.tetlet.2014.10.086
Wang, G.; Shen, R.; Xu, Q.; Goto, M.; Zhao, Y.; Han, L.-B. Stereospecific Coupling of H-Phosphinates and Secondary Phosphine Oxides with Amines and Alcohols: A General Method for the Preparation of Optically Active Organophosphorus Acid Derivatives. J. Org. Chem. 2010, 75, 3890- 3892, 10.1021/jo100473s
Stiles, A. R.; Vaughan, W. E.; Rust, F. F. The Preparation of Dialkyl Alkylphosphonates by Addition of Dialkyl Phosphites to Olefins. J. Am. Chem. Soc. 1958, 80, 714- 716, 10.1021/ja01536a048
Keglevich, G.; Sipos, M.; Takács, D.; Greiner, I. A Study on the Michael Addition of Dialkylphosphites to Methylvinylketone. Heteroat. Chem. 2007, 18, 226- 229, 10.1002/hc.20266
Kim, S. H.; Kim, S. H.; Kim, H. J.; Kim, J. N. An Efficient Conjugate Addition of Dialkyl Phosphite to Electron-Deficient Olefins: The Use of a Nucleophilic Organocatalyst to Form a Strong Base. Bull. Korean Chem. Soc. 2013, 34, 989- 992, 10.5012/bkcs.2013.34.3.989
Thielges, S.; Bisseret, P.; Eustache, J. Copper-Mediated Cross-Coupling of H-Phosphonates with Vinyliodonium Salts: A Novel Very Mild Synthesis of 2-Arylvinylphosphonates. Org. Lett. 2005, 7, 681- 684, 10.1021/ol047516y
Abrunhosa-Thomas, I.; Sellers, C. E.; Montchamp, J.-L. Alkylation of H-Phosphinate Esters under Basic Conditions. J. Org. Chem. 2007, 72, 2851- 2856, 10.1021/jo062436o
Gavara, L.; Petit, C.; Montchamp, J.-L. DBU-Promoted Alkylation of Alkyl Phosphinates and H-Phosphonates. Tetrahedron Lett. 2012, 53, 5000- 5003, 10.1016/j.tetlet.2012.07.019
Jablonkai, E.; Keglevich, G. P-C Bond Formation by Coupling Reactions Utilizing >P(O)H Species as the Reagents. Curr. Org. Synth. 2014, 11, 429- 453, 10.2174/15701794113109990066
Kalek, M.; Stawinski, J. Pd(0)-Catalyzed Phosphorus-Carbon Bond Formation. Mechanistic and Synthetic Studies on the Role of the Palladium Sources and Anionic Additives. Organometallics 2007, 26, 5840- 5847, 10.1021/om700797k
Henyecz, R.; Keglevich, G. New Developments on the Hirao Reactions, Especially from “Green” Point of View. Curr. Org. Synth. 2019, 16, 523- 545, 10.2174/1570179416666190415110834
Hosseinian, A.; Hosseini Nasab, F. A.; Ahmadi, S.; Rahmani, Z.; Vessally, E. Decarboxylative Cross-Coupling Reactions for P(O)-C Bond Formation. RSC Adv. 2018, 8, 26383- 26398, 10.1039/C8RA04557G
Hu, G.; Gao, Y.; Zhao, Y. Copper-Catalyzed Decarboxylative C-P Cross-Coupling of Alkynyl Acids with H-Phosphine Oxides: A Facile and Selective Synthesis of (E)-1-Alkenylphosphine Oxides. Org. Lett. 2014, 16, 4464- 4467, 10.1021/ol502009b
Wu, Y.; Liu, L. L.; Yan, K.; Xu, P.; Gao, Y.; Zhao, Y. Nickel-Catalyzed Decarboxylative C-P Cross-Coupling of Alkenyl Acids with P(O)H Compounds. J. Org. Chem. 2014, 79, 8118- 8127, 10.1021/jo501321m
Chen, Z. S.; Zhou, Z. Z.; Hua, H. L.; Duan, X. H.; Luo, J. Y.; Wang, J.; Zhou, P. X.; Liang, Y. M. Reductive Coupling Reactions: A New Strategy for C(sp3)-P Bond Formation. Tetrahedron 2013, 69, 1065- 1068, 10.1016/j.tet.2012.11.064
Miao, W.; Gao, Y.; Li, X.; Gao, Y.; Tang, G.; Zhao, Y. Copper-Catalyzed Synthesis of Alkylphosphonates from H-Phosphonates and N-Tosylhydrazones. Adv. Synth. Catal. 2012, 354, 2659- 2664, 10.1002/adsc.201200295
Wu, L.; Zhang, X.; Chen, Q.-Q.; Zhou, A.-K. A Novel Copper-Catalyzed Reductive Coupling of N-Tosylhydrazones with H-Phosphorus Oxides. Org. Biomol. Chem. 2012, 10, 7859- 7862, 10.1039/c2ob26414e
Bhattacharya, A. K.; Thyagarajan, G. Michaelis-Arbuzov Rearrangement. Chem. Rev. 1981, 81, 415- 430, 10.1021/cr00044a004
Wang, Z. Comprehensive Organic Name Reactions and Reagents; Hoboken, N. J., Ed.; John Wiley & Sons, Inc.: US, 2010.
Michaelis, A.; Kaehne, R. Ueber Das Verhalten Der Jodalkyle Gegen Die Sogen. Phosphorigsäureester Oder O-Phosphine. Ber. Dtsch. Chem. Ges. 1898, 31, 1048- 1055, 10.1002/cber.189803101190
Arbuzov, A. E.; Arbuzov, I. J. Russ. Phys. Chem. Soc. 1906, 38, 687
Arbuzov, A. E. Chem. Zentr. 1906, 1639
Ma, X.; Xu, Q.; Li, H.; Su, C.; Yu, L.; Zhang, X.; Cao, H.; Han, L.-B. Alcohol-Based Michaelis-Arbuzov Reaction: An Efficient and Environmentally-Benign Method for C-P(O) Bond Formation. Green Chem. 2018, 20, 3408- 3413, 10.1039/C8GC00931G
Jansa, P.; Holý, A.; Dračinský, M.; Baszczyňski, O.; Česnek, M.; Janeba, Z. Efficient and “green” Microwave-Assisted Synthesis of Haloalkylphosphonates via the Michaelis-Arbuzov Reaction. Green Chem. 2011, 13, 882- 888, 10.1039/c0gc00509f
Kiddle, J. J.; Gurley, A. F. Microwave irradiation in organophosphorus chemistry 1: the Michaelis-Arbuzov reaction. Phosphorus, Sulfur Silicon Relat. Elem. 2000, 160, 195- 205, 10.1080/10426500008043680
Villemin, D.; Simeon, F.; Decreus, H.; Jaffres, P.-A. Rapid and efficient arbuzov reaction under microwave irradiation. Phosphorus, Sulfur Silicon Relat. Elem. 1998, 133, 209- 213, 10.1080/10426509808032465
Ravikumar, D.; Subramanyam, C.; Mohan, S.; Chandra Sekhar, D.; Prasada Rao, K. Nano BF3.SiO2 Catalysed, Microwave Assisted Michaelis-Arbuzov Reaction to Synthesize Biologically Active Phosphonates under Solvent-Free Condition. Mater. Today Proc. 2018, 5, 25832- 25842, 10.1016/j.matpr.2018.06.576
Ghosh, S.; Biswas, K.; Basu, B. Recent Advances in Microwave Promoted C-P Cross-Coupling Reactions. Curr. Microwave Chem. 2020, 7, 112- 122, 10.2174/2213335607666200401144724
De La Hoz, A.; Alcázar, J.; Carillo, J.; Herrero, M. A.; De Muoz, J. M.; Prieto, P.; De Cózar, A.; Diaz-Ortiz, A. Reproducibility and Scalability of Microwave-Assisted Reactions. In Microwave Heating; InTech, 2011.
Plutschack, M. B.; Pieber, B.; Gilmore, K.; Seeberger, P. H. The Hitchhiker’s Guide to Flow Chemistry. Chem. Rev. 2017, 117, 11796- 11893, 10.1021/acs.chemrev.7b00183
Morodo, R.; Bianchi, P.; Monbaliu, J.-C. M. Continuous Flow Organophosphorus Chemistry. Eur. J. Org. Chem. 2020, 2020, 5236- 5277, 10.1002/ejoc.202000430
Gérardy, R.; Emmanuel, N.; Toupy, T.; Kassin, V. E.; Tshibalonza, N. N.; Schmitz, M.; Monbaliu, J.-C. M. Continuous Flow Organic Chemistry: Successes and Pitfalls at the Interface with Current Societal Challenges. Eur. J. Org. Chem. 2018, 20-21, 2301- 2351, 10.1002/ejoc.201800149
Glasnov, T. N.; Kappe, C. O. The Microwave-to-Flow Paradigm: Translating High-Temperature Batch Microwave Chemistry to Scalable Continuous-Flow Processes. Chem. A Eur. J. 2011, 17, 11956- 11968, 10.1002/chem.201102065
Jasiak, A.; Mielniczak, G.; Owsianik, K.; Koprowski, M.; Krasowska, D.; Drabowicz, J. Solvent-Free Michaelis-Arbuzov Rearrangement under Flow Conditions. J. Org. Chem. 2019, 84, 2619- 2625, 10.1021/acs.joc.8b03053
Watson, W. On Byproducts and Side Products. Org. Process Res. Dev. 2012, 16, 1877- 1877, 10.1021/op300317g
Toupy, T.; Kune, C.; Van Hecke, K.; Quinton, L.; Monbaliu, J.-C. M. A Multifaceted Approach towards Understanding the Peculiar Behavior of (α)-Hydroxyiminophosphonates. Org. Chem. Front. 2021, 9, 173- 182, 10.1039/D1QO01564H
Kassin, V.-E. H.; Morodo, R.; Toupy, T.; Jacquemin, I.; Van Hecke, K.; Robiette, R.; Monbaliu, J.-C. M. A Modular, Low Footprint and Scalable Flow Platform for the Expedient α-Aminohydroxylation of Enolizable Ketones. Green Chem. 2021, 23, 2336- 2351, 10.1039/D0GC04395H
Morodo, R.; Gérardy, R.; Petit, G.; Monbaliu, J.-C. M. Continuous Flow Upgrading of Glycerol toward Oxiranes and Active Pharmaceutical Ingredients Thereof. Green Chem. 2019, 21, 4422- 4433, 10.1039/C9GC01819K
Kassin, V.-E. H.; Gérardy, R.; Toupy, T.; Collin, D.; Salvadeo, E.; Toussaint, F.; Van Hecke, K.; Monbaliu, J.-C. M. Expedient Preparation of Active Pharmaceutical Ingredient Ketamine under Sustainable Continuous Flow Conditions. Green Chem. 2019, 21, 2952- 2966, 10.1039/C9GC00336C
Kozlowski, L. P. Proteome-pI Proteome Isoelectric Point Database. Nucleic Acids Res. 2017, 45, D1112- D1116, 10.1093/nar/gkw978
Justyna, K.; Małolepsza, J.; Kusy, D.; Maniukiewicz, W.; Błażewska, K. M. The McKenna Reaction - Avoiding Side Reactions in Phosphonate Deprotection. Beilstein J. Org. Chem. 2020, 16, 1436- 1446, 10.3762/bjoc.16.119
Błazewska, K. M. McKenna Reaction - Which Oxygen Attacks Bromotrimethylsilane?. J. Org. Chem. 2014, 79, 408- 412, 10.1021/jo4021612
Fukuyama, T.; Chiba, H.; Kuroda, H.; Takigawa, T.; Kayano, A.; Tagami, K. Application of Continuous Flow for DIBAL-H Reduction and n-BuLi Mediated Coupling Reaction in the Synthesis of Eribulin Mesylate. Org. Process Res. Dev. 2016, 20, 503- 509, 10.1021/acs.oprd.5b00353
Gaussian 09, Revision D.01, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian, Inc.: Wallingford CT, 2009.