Our group's research interests are in the areas of organophosphorus chemistry, and bioorganic/medicinal chemistry. The element phosphorus is the common thread throughout our research projects. The core of our program in phosphorus-based chemical biology focuses on the mechanism-based design, synthesis and evaluation of biologically active molecules such as enzyme inhibitors, and the development of novel antisense oligonucleotides with emphasis on the application of automated synthesis and combinatorial techniques whenever possible. Unnatural compounds are synthesized to probe various biological processes. Applications of this research range from the elucidation of enzyme mechanisms to the preparation of molecules with potential medicinal use (anticancer, antiparasite, immuno suppressant, antisense, GABA analogues). One such medicinally oriented goal is the preparation and evaluation of new hydrolytically stable “antisense oligonucleotides” for sequence specific complexation to RNA and DNA targets (such as peptide nucleic acids (PNAs)/phosphinate hybrids). We are also interested in 1,1-bisphosphorus compounds as pyrophosphate analogs, since pyrophosphate has a rich biochemical role. Finally, other investigations aiming at the modulation of GABA receptors with phosphinic analogues are relevant to the treatment of various central nervous system (CNS) disorders. With TCU’s Professor Coffer, we have also been preparing and evaluating components for biocompatible calcified nanoporous. In general, because phosphorus compounds are ubiquitous in living systems, the synthesis of phosphorus-containing mimics can have important medicinal benefits. Our second research interest concerns organophosphorus chemistry and is driven by several main objectives: firstly, the development of P-chiral ligands to be ultimately used in catalytic asymmetric transformations, including transition metal-catalyzed reactions; secondly, the building of a methodology to produce phosphorus compounds in general; and thirdly, the preparation of compounds possessing potential biological activity. Our expertise lies in the area of hypophosphorous compounds and their derivatives (H-phosphinates and phosphinates, and to a lesser extent phosphonates). One area of significant current interest in the laboratory, is the development of sustainable synthetic methodologies to avoid phosphorus trichloride (PCl3). Our program toward the development of new methodology for the synthesis of phosphinic acids has led to many novel reactions, including the palladium-catalyzed cross-coupling of hypophosphite derivatives with aryl, benzylic, and alkenyl electrophiles, and the room temperature radical addition of hypophosphites to olefins. These reactions are also applied to the synthesis of biologically active compounds, to the preparation of intermediates with industrial value, and to the preparation of P-chiral building blocks. Combining the above research directions into the same program provides valuable advantages. Because phosphorus is ubiquitous in nature, a variety of molecules can be designed to achieve some specific biological effect. To achieve the efficient synthesis of such compounds, new synthetic routes are required, which borrow from independently developed methodologies. In general, a combination of organic synthesis, methodology, and chemical biology, is used to pursue our objectives.

Graphical Methodological Summary

Pyrophosphate Analogs

Research Highlights

CONGRATULATIONS TO PROFESSOR Ei-ichi NEGISHI, 2010 WINNER OF THE CHEMISTRY NOBEL PRIZE!

PUBLICATIONS

“Preparation of a Clickable Monomer Compatible with Automated PNA Synthesis” Newell, G. E.; Sabourin, A.; Montchamp, J.-L. Tetrahedron Lett. 2021, 68, Article in Press.

“Evaluation and Development of Methodologies for the Synthesis of Thiophosphinic Acids” Winters, K. R.; Montchamp, J.-L. J. Org. Chem. 2020, 85, 14545-14558.

“Manganese-Catalyzed and Mediated Synthesis of Arylphosphinates and Related Compounds” Berger, O.; Montchamp, J.-L. J. Org. Chem. 2019, 84, 9239-9256.

“On the Cost of Academic Methodologies” Berger, O.; Winters, K. R.; Sabourin, A.; Dzyuba, S. V.; Montchamp, J.-L. Org. Chem. Front. 2019, 6, 2095-2108.

“Challenges and solutions in phosphinate chemistry” Montchamp, J.-L. Pure Appl. Chem. 2019, 91, 113-120.

“Manganese-Mediated Homolytic Aromatic Substitution With Phosphinylidenes” Berger, O.; Montchamp, J.-L. Chem. Rec. 2017, 17, 1-17.

“Palladium-Catalyzed Allylation/Benzylation of H-Phosphinate Esters with Alcohols” Fers-Lidou, A.; Berger, O.; Montchamp, J.-L. Molecules 2016, 21, 1295-1310.

“General Synthesis of P-Stereogenic Compounds: The Menthyl Phosphinate Approach” Berger, O.; Montchamp, J.-L. Org. Biomol. Chem. 2016, 14, 7552-7562.

“P(=O)H to P-OH Tautomerism: A Theoretical and Experimental Study” Janesko, B. J.; Fisher, H. C.; Bridle, M. J.; Montchamp, J.-L. J. Org. Chem. 2015, 80, 10025-10032.

“Development of a New Family of Chiral Auxiliary” Gelat, F.; Richard, V.; Berger, O; Montchamp, J.-L. Org. Lett. 2015, 17, 1819-1821.

“Manganese-Mediated Alkene Chloro-Phosphinoylation” Richard, V.; Fisher, H. C.; Montchamp, J.-L. Tetrahedron Lett. 2015, , online.

“Carbon-Hydrogen to Carbon-Phosphorus Transformations” Montchamp, J.-L. Top. Curr. Chem. 2015, 361, 217-252.

“Synthesis of (phosphonomethyl)phosphinate pyrophosphate analogues via the phospha-Claisen condensation” Gelat, F.; Lacomme, C.; Berger, O; Gavara, L.; Montchamp, J.-L. Org. Biomol. Chem. 2015, 13, 825-833.

"Radical Arylation of H-Phosphinates and Related Compounds” Berger, O.; Montchamp, J.-L. Chem. Eur. J. 2014, 20 , 12385.

“Phosphinate-Containing Heterocycles: a Mini-Review” Berger, O.; Montchamp, J.-L. Beilstein J. Org. Chem. 2014, 10 , 732.

“Manganese-Catalyzed and Promoted Reactions of H-Phosphinate Esters” Fisher, H. C.; Berger, O.; Gelat, F. Montchamp, J.-L. Adv. Synth. Catal. 2014, 356 , 1199.

“Phosphinate Chemistry in the 21st Century: A Viable Alternative to the Use of Phosphorus Trichloride in Organophosphorus Synthesis” Montchamp, J.-L. Acc. Chem. Res. 2014, 47, 77

“Organophosphorus Chemistry Without PCl3: A Bridge From Hypophosphorous Acid to H-Phosphonate Diesters” Fisher, H. C.; Prost, L.; Montchamp, J.-L. Eur. J. Org. Chem. 2013, ,7973.

“A General Strategy for the Synthesis of P-Stereogenic Compounds” Berger, O.; Montchamp, J.-L. Angew. Chem. Int. Ed. 2013, 52,11377. (HOT PAPER)

“Hypophosphorous Acid, Second Update” Gelat, F.; Montchamp, J.-L. Encyclopedia of Reagents for Organic Synthesis (eEROS) , ,

“Phosphinic acid, P-(hydroxymethyl)-” Berger, O..; Montchamp, J.-L. Encyclopedia of Reagents for Organic Synthesis (eEROS) , ,

“Hydrophosphinylation of Unactivated Terminal Alkenes Catalyzed by Nickel Chloride” Ortial, S.; Fisher, H. C.; Montchamp, J.-L. J. Org. Chem. 2013, 78, 6599

“Phosphorus-Carbon Bond Formation: Palladium-Catalyzed Cross-Coupling of H-Phosphinates and Other P(O)H-Containing Compounds” Berger, O.; Petit, C.; Deal E. L.; Montchamp, J.-L. Adv. Synth. Catal. 2013, 355, 1361

“The Phosphorus-Claisen Condensation” Gavara, L.; Gelat, F.; Montchamp, J.-L. Tetrahedron. Lett. 2013, 54, 817

“Organophosphorus Synthesis Without Phosphorus Trichloride: The Case For The Hypophosphorous Pathway” Montchamp, J.-L. Phosphorus, Sulfur and Silicon and the Related Elements 2013, 188, 66

“DBU-Promoted Alkylation of Alkyl Phosphinates and H-Phosphonates” Gavara, L.; Petit, C.; Montchamp, J.-L. Tetrahedron Lett. 2012, 53, 5000

“Chemistry of the versatile (hydroxymethyl)phosphinyl P(O)CH2OH functional group” Berger, O.; Gavara, L.; Montchamp, J.-L. Org. Lett. 2012, 14, 3404

“Synthesis of Disubstituted Phosphinates via Palladium-Catalyzed Hydrophosphinylation of H-Phosphinic Acids” Petit, C.; Fécourt, F.; Montchamp, J.-L. Adv. Synth. Catal. 2011, 353, 1883

“Palladium-Catalyzed Cross-Coupling of H-Phosphinate Esters with Chloroarenes” Deal, E. L.; Petit, C.; Montchamp, J.-L. Org. Lett. 2011, 13, 3270

“Synthesis of Z-Alkenyl Phosphorus Compounds Through Hydroalumination and Carbocupration of Alkynyl Precursors” Ortial, S.; Montchamp, J.-L. Org. Lett. 2011, 13, 3134

“Silver-free synthesis of nitrate-containing room-temperature ionic liquids” Smith, N. W.; Gourisankar, S. P.; Montchamp, J.-L.; Dzyuba, S. V. New. J. Chem. 2011, 35, 909

“Regiocontrol in the Palladium-Catalyzed Hydrophosphinylation of Terminal Alkynes” Belabassi, Y.; Bravo-Altamirano, K.; Montchamp, J.-L. J. Organomet. Chem. 2011, 696, 106

“Mixed 1,1-Bis-Phosphorus Compounds: Synthesis, Alkylation, and Horner-Wadsworth-Emmons Olefination Reactions” Ortial, S.; Thompson, D. A.; Montchamp, J.-L. J. Org. Chem. 2010, 75, 8166

“Strategies for the asymmetric synthesis of H-phosphinate esters” Bravo-Altamirano, K.; Coudray, L.; Montchamp, J.-L. Org. Biomol. Chem. 2010, 8, 5541

“Synthesis and Reactivity Studies of a,a-Difluoromethylphosphinates” Abrunhosa-Thomas, I.; Coudray, L.; Montchamp, J.-L. Tetrahedron 2010, 66, 4434

“Facile P,N-heterocycles synthesis via tandem aminomethylation-cyclization of H-phosphinates building blocks” Queffelec, C.; Montchamp, J.-L. Org. Biomol. Chem. 2010, 8, 267

“Synthesis and In Vitro Evaluation of Aspartate Transcarbamoylase Inhibitors” Coudray, L.; Pennebaker, A. F.; Montchamp, J.-L. Bioorg. Med. Chem. 2009, 17, 7680

“Temporary Protection of H-Phosphinic Acids as a Synthetic Strategy” Coudray, L.; Montchamp, J.-L. Eur. J. Org. Chem. 2009, 4646

“Reactions of a-Boranophosphorus Compounds with Electrophiles: Alkylation, Acylation, and other Reactions” Antczak, M. I.; Montchamp, J.-L. J. Org. Chem 2009, 74, 3758

“Prodrug Surface Modification of Silicon Nanowires: Impact on Calcification and Stromal Cell Proliferation” Jiang, K.; Fan, D.; Belabassi, Y.; Akkaraju, G.; Montchamp, J.-L.; Coffer, J. L. ACS Appl. Mat. Interfaces 2009, 1, 266

“Submicromolar Phosphinic Inhibitors of E. coli Aspartate Transcarbamoylase” Coudray, L.; Kantrowitz, E. R.; Montchamp, J.-L. Bioorg. Med. Chem. Lett. 2009, 19, 900

“A Facile Synthesis and Crystallographic Analysis of Seven Trityl Phosphorus Compounds and Two Nickel(II) Phosphine Side-Products” Gushwa, A. F.; Belabassi, Y.; Montchamp, J.-L., Richards, A. F. J. Chem. Cryst. 2009, 39, 337

“Synthesis of P,N-Heterocycles from w-Amino-H-Phosphinates: Conformationally Restricted a-Aminoacid Analogs” Queffelec, C.; Ribière, P.; Montchamp, J.-L. J. Org. Chem. 2008, 73, 8987

“Synthesis of 1,1-Bis-Phosphorus Compounds from Organoboranes” Antczak, M. I.; Montchamp, J.-L. Tetrahedron Lett. 2008, 49, 5909

“Revisiting the Hirao Cross-Coupling: Improved Synthesis of Aryl & Heteroaryl Phosphonates” Belabassi, Y.; Alzghari, S.; Montchamp, J.-L. J. Organomet. Chem. 2008, 693, 3171

“5-Pyrimidyl Phosphonic Acid as a Building Block for the Synthesis of Coordination Polymers” Samanamu, C. R.; Zamora, E. N.; Lesikar, L. A.; Montchamp, J.-L.; Richards, A. F. Cryst. Eng. Comm. 2008, 10, 1372

“Borane Complexes of the H3PO2 P(III) Tautomer: Useful Phosphinate Equivalents” Belabassi, Y.; Antczak, M. I.; Tellez, J.; Montchamp, J.-L. Tetrahedron 2008, 64, 9181

“Green, Palladium-Catalyzed Synthesis of Benzylic H-Phosphinates from Hypophosphorous Acid and Benzylic Alcohols” Coudray, L.; Montchamp, J.-L. Eur. J. Org. Chem. 2008, 4101

“Recent Developments in the Addition of Phosphinylidene-Containing Compounds to Unactivated Unsaturated Hydrocarbons: Phosphorus-Carbon Bond-Formation via Hydrophosphinylation and Related Processes” Coudray, L.; Montchamp, J.-L. Eur. J. Org. Chem. 2008, 3601

“Structural Analogues of Bioactive Phosphonic Acids: First Crystal Structure Characterization of Phosphonothioic and Boranophosphonic Acids” Belabassi, Y.; Gushwa, A. F.; Richards, A. F.; Montchamp, J.-L. Phosphorus, Sulfur and Silicon and the Related Elements 2008, 183, 2214

“Synthesis of Homo and Hetero Metal-Phosphonate Frameworks from Bi-Functional Aminomethylphosphonic acid” Samanamu, C. R.; Zamora, E. N.; Montchamp, J.-L.; Richards, A. F. J. Solid State Chem. 2008, 181, 1462

“Allylic Phosphinates via Palladium-Catalyzed Allylation of H-Phosphinic Acids with Allylic Alcohols”Coudray, L.; Bravo-Altamirano, K.; Montchamp, J.-L.. Org. Lett. 2008, 10, 1123

“Mild Synthesis of Organophosphorus Compounds: Reaction of Phosphorus-Containing Carbenoids with Organoboranes” Antczak, M. I.; Montchamp, J.-L. Org. Lett. 2008, 10, 977.

“Palladium-Catalyzed Reactions of Hypophosphorous Compounds with Allenes, Dienes and Allylic Electrophiles: Methodology for the Synthesis of Allylic-H-Phosphinates” Bravo-Altamirano, K.; Abrunhosa-Thomas, I.; Montchamp, J.-L. J. Org. Chem. 2008, 73, 2292

“ Convenient Synthesis of Aluminum and Gallium Phosphonate Cages” Samanamu, C. R.; Olmstead, M. M.; Montchamp, J.-L.; Richards, A. F. Inorg. Chem. 2008, 47, 3879

“Palladium-Catalyzed Dehydrative Allylation of Hypophosphorous Acid with Allylic Alcohols. Preparation of Cinnamyl-H-Phosphinic Acid” Bravo-Altamirano, K.; Montchamp, J.-L. Org. Synth. 2008, 85, 96

“A Mild Synthetic Route to Zinc, Cadmium, and Silver Polymers with 2-Pyridyl Phosphonic Acid: Synthesis and Analysis ” Fry, J. A.; Samanamu, C. R.; Montchamp, J.-L.; Richards, A. F. Eur. J. Inorg. Chem. 2008, 463

“New Access to H-Phosphonates via Metal-Catalyzed Phosphorus-Oxygen Bond Formation” Coudray, L.; Abrunhosa-Thomas, I.; Montchamp, J.-L. Tetrahedron Lett. 2007, 48, 6505

“A Novel Approach to Phosphonic Acids from Hypophosphorous acid” Bravo-Altamirano, K., Montchamp, J.-L. Tetrahedron Lett. 2007, 48, 5755.

“Alkylation of H-Phosphinate Esters under Basic Conditions” Abrunhosa-Thomas, I.; Sellers, C. E., Montchamp, J.-L. J. Org. Chem. 2007, 72, 2851.

“AIBN-initiated Radical Reactions of Ethyl Phosphinate” Antczak, M. I.; Montchamp, J.-L. Synthesis 2006, 3080.

“Palladium-Catalyzed Dehydrative Allylation of Hypophosphorous Acid with Allylic Alcohols” Bravo-Altamirano, K.; Montchamp, J.-L. Org. Lett. 2006, 8, 4169.

“Advances in the Synthesis of H-Phosphinic Acids and Esters” Montchamp, J.-L. Specialty Chemicals Magazine 2006, 26, 44.

"Direct Monoalkylation of Alkyl Phosphinates to Access H-Phosphinic Acid Esters”
Abrunhosa-Thomas, I.; Ribière, P.; Adcock, A. C.; Montchamp, J.-L. Synthesis 2006, 325.

“Radical Reaction of Sodium Hypophosphite with Terminal Alkynes: Synthesis of 1,1-bis-H-Phosphinates”
Gouault-Bironneau, S.; Deprèle, S.; Sutor, A.; Montchamp, J.-L. Org. Lett. 2005, 7, 5909.

“Palladium-Catalyzed Phosphorus-Carbon Bond Formation: Cross-Coupling Reactions of Alkyl Phosphinates with Aryl, Heteroaryl, Alkenyl, Benzylic, and Allylic Halides and Triflates”
Bravo-Altamirano, K.; Huang, Z.; Montchamp, J.-L. Tetrahedron 2005,61, 6315.

"NiCl2-Catalyzed Hydrophosphinylation", Ribiere, P.; Bravo-Altamirano, K.; Antczak, M. I.; Hawkins, J. D.; Montchamp, J.-L. J. Org. Chem. 2005, 70, 4064.

"Recent Advances in Phosphorus-Carbon Bond Formation: Synthesis of H-Phosphinic Acid Derivatives from Hypophosphorous Compounds", Montchamp, J.-L. J. Organomet. Chem., 2005, 690, 2388

"Environmentally Benign Synthesis of H-Phosphinic Acids Using a Water-Tolerant, Recyclable Polymer-Supported Catalyst", Deprèle, S.; Montchamp, J.-L. Org. Lett. 2004, 6, 3805.

"Direct Synthesis of H-Aryl and H-Heteroarylphosphinic Esters via Palladium-Catalyzed Cross-Coupling of Alkylphosphinates", Huang, Z.; Bravo-Altamirano, K.; Montchamp, J.-L. Comptes Rendus Chimie 2004, 7/8-9, 763.

"Routes to Calcified Porous Silicon: Implications for Drug Delivery and Biosensing", Coffer, J. L.; Montchamp, J.-L.; Aimone, J. B.; Weis, R. P. Physica Status Solidi (a) 2003, 197, 336.

"Calcified Nanostructured Silicon Wafer Surfaces for Biosensing: Effects of Surface Modification on Bioactivity", Weis, R. P.; Montchamp, J.-L.; Coffer, J. L.; Desai, T. A.; Atthia, D. G. Disease Markers 2002, 18, 159.

"Palladium-Catalyzed Hydrophosphinylation of Alkenes and Alkynes", Deprèle, S.; Montchamp, J.-L. J. Am. Chem. Soc. 2002, 124, 9386.

"Palladium-Catalyzed Cross-Coupling Reaction of Anilinium Hypophosphite With Alkenyl Bromides and Triflates: Application to the Synthesis of GABA Analogs", Dumond, Y. R.; Montchamp, J.-L. J. Organomet. Chem. 2002, 653, 252.

"A Novel and Convenient Preparation of Hypophosphite Esters", Deprèle, S.; Montchamp, J.-L. J. Organomet. Chem. 2002, 643-644, 154.

"Triethylborane-Initiated Room Temperature Radical Addition of Hypophosphites to Olefins: Synthesis of Monosubstituted Phosphinic Acids and Esters", Deprèle, S.; Montchamp, J.-L. J. Org. Chem. 2001, 66, 6745.

"Synthesis of Monosubstituted Phosphinic Acids: Palladium-Catalyzed Cross-Coupling Reactions of Anilinium Hypophosphite", Montchamp, J.-L.; Dumond, Y. R. J. Am. Chem. Soc. 2001, 123, 510.

"Orthosilicate-Mediated Esterification of Monosubstituted Phosphinic Acids", Dumond, Y. R.; Baker, R. L.; Montchamp, J.-L. Org. Lett. 2000, 2, 3341.