From masked carbenes to heterocycles: Novel potentially biological active difluoromethylene phosphonates as versatile building blocks
Final Report Abstract
The phosphate moiety is a common structural fragment present in a wide range of biologically active compounds. In addition, α,α-difluoromethylenphosphonates are very important analogues of natural phosphates and have been found to be, for example, valuable enzyme inhibitors. Diazo compounds are, in turn, remarkably versatile building blocks in organic synthesis and their chemistry is still far from losing anything of its long-standing fascination and the inventory of methods for the preparation of a variety of diazo compounds is continuously supplemented by new methods and novel variations of established procedures. In this context, successful synthesis of a series of 2-diazo-1,1-difluoroalkyl phosphonates, upon diazotization of appropriate amines with tert-butyl nitrite in the presence of acetic acid, has been for the first time achieved. To exploit the rich chemistry of the diazo group as a versatile building block we subsequently used novel diazo derivatives in several different reactions, namely in O-H insertions with carboxylic, sulfonic acids and alcohols, cyclopropanation, Doyle-Kirmse rearrangement, [3+2] cycloaddition reactions as well as chlorination and aza-Wittig reaction. As a result, we were able to obtain a series of novel esters, cyclopropanes, sulfides, pyrazoles and pyrazolines possessing a difluromethyl phosphonate function. Unexpectedly, in the O-H insertion reaction of alcohols to 2-diazo-1,1,3,3,3-pentafluoropropyl phosphonate as well as in the aza-Wittig reaction with aryl 2-diazo-1,1-difluoropropyl phosphonates, α-fluorovinyl phosphonates were obtained as sole products. The presented chemistry opens the possibility for further modifications and application, especially in material or medicinal chemistry and represent an important achievement to the chemistry of fluorinated diazo molecules.
Publications
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Chemistry of electrochemical oxidative reactions of sulfinate salts, Green Chemistry, 2020, 22, 3028-3059
H. Mei, R. Pajkert, L. Wang, G.- V. Röschenthaler, J. Han
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Selectfluor-promoted oxidative reaction of disulfides and amines: access to sulfinamides, Organic & Biomolecular Chem., 2020, 18, 3761-3766
H. Mei, J. Liu, R. Pajkert, G.-V. Röschenthaler, J. Han
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Selectfluor-promoted twofold sulfination of alcohols for synthesis of sulfinic ester from diaryl disulfides, Chinese J. Org. Chem., 2020, 40, 1926-1933
Aiyao Liu, Jiang Liu, Haibo Mei, G.-V. Röschenthaler, Jianlin Han, Youji Huaxue
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[3+2] Cycloaddition Reactions of β-Diazo-α,α-difluoromethylphosphonates with α,β-Unsaturated Esters, J. Fluorine Chem. 2021, 251, 109899
Q. Wang, L. Wang, R. Pajkert, I. Hajdin, J. Liu, H. Mei, G.-V. Röschenthaler, J. Han
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Design of (β-diazo-α,α-difluoroethyl) phosphonates and their application as masked carbenes in visible light-promoted coupling reactions with sulfonic acids, Org. Chem. Frontiers 2021, 8(4), 767-772
H. Mei, J. Liu, R. Pajkert, L. Wang, G.-V. Röschenthaler, J. Han
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Esterification of carboxylic acids with (β-diazo-α,α-difluoroethyl)phosphonates under photochemical conditions, Acta Chim. Sinica, 2021, 79, 747-750
J. Liu, J. Xu, R. Pajkert, H. Mei, G.-V. Röschenthaler, J. Han
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In Situ Generation of Unstable Difluoromethylphosphonate-Containing Di-azoalkanes and Their Use in [3 + 2] Cycloaddition Reactions with Vinyl Sulfones, Org. Lett., 2021, 23, 1130−1134
H. Mei, L. Wang, R. Pajkert, Q. Wang, J. Xu, J. Liu, G.-V. Röschenthaler, J. Han
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VIP: Recent Advances in Synthesis of Difluoromethylene Phosphonates for Biological Applications, Adv. Synth. & Cat., 2021, 363, 2912–2968
M. Shevchuk, Q. Wang, R. Pajkert, J. Xu, H. Mei, G.-V. Röschenthaler, J. Han
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Facile synthesis of (β-chlorodifluoroethyl)phosphonates via chlorination reaction of difluoroalkyl diazo derivatives with HCl, Chinese Chem. Lett., 2022, 33, 2429–2432
J. Liu, R. Pajkert, L. Wang, H. Mei, G.-V. Röschenthaler, J. Han
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One‐Pot Reaction of (β‐Amino‐α,α‐difluoroethyl)phosphonates with Trifluoromethylated Ketones via Aza‐Wittig Reagents, Adv. Synth. & Cat., 2022
Haibo Mei, Qian Wang, R. Pajkert, Jiang Liu, G.-V. Röschenthaler, Jianlin Han
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Science of Synthesis, Vol. 42 (update 2020), 42.18. Product Class 18: Pentacoordinated Phosphoranes, Science of Synthesis Knowledge Updates, 2022, 1, 365-393
R. Pajkert, G.-V. Röschenthaler
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Science of Synthesis, Vol. 42 (update 2020), 42.19. Product Class 19: Hexacoordinated Phosphates, Science of Synthesis Knowledge Updates, 2022, 1, 395-412
R. Pajkert, G.-V. Röschenthaler
