Synthesis and spectral properties of α,α-difluorinated β-iminophosphonates

Rapp, Magdalena; Szewczyk, Marta Z.; Koroniak, Henryk

doi:10.1016/j.jfluchem.2014.07.008

Cited by 7 publications

(3 citation statements)

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“…We initiated the sequence by the condensation of diethyl ß -ketophosphonate 1 with a series of primary amines, respectively, ( S )- and ( R )- α -methylbenzylamine (MBn-NH 2 ), p -methoxybenzylamine (PMB-NH 2 ), and p -methoxyphenylamine (PMP-NH 2 ). These reactions resulted in a tautomeric mixture of major β -enaminophosphonates ( 2 – 5 ) and minor β -iminophosphonates ( 6 – 9 ) [ 54 , 55 ]. When p -methoxyphenylamine was used, the ratio of enamine ( Z )/imine ( E : Z ) 5a / 9a,b was 1/0.53 (1:0.1), as determined by 31 P NMR.…”

Section: Resultsmentioning

confidence: 99%

Access to 2-Fluorinated Aziridine-2-phosphonates from α,α-Halofluorinated β-Iminophosphonates—Spectroscopic and Theoretical Studies

et al. 2023

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The efficient one-pot halofluorination of a β-enaminophosphonate/β-iminophosphonate tautomeric mixture resulting in α,α-halofluorinated β-iminophosphonates is reported. Subsequent imine reduction gave the corresponding β-aminophosphonates as a racemic mixture or with high diastereoselectivity. The proposed protocol is the first example of a synthesis of N-inactivated aziridines substituted by a fluorine and phosphonate moiety on the same carbon atom. Based on spectroscopic and theoretical studies, we determined the cis/trans geometry of the resulting fluorinated aziridine-2-phosphonate. Our procedure, involving the reduction of cis/trans-fluoroaziridine mixture 24, allows us to isolate chiral trans-aziridines 24 as well as cis-aziridines 27 that do not contain a fluorine atom. We also investigated the influence of the fluorine atom on the reactivity of aziridine through an acid-catalyzed regioselective ring-opening reaction. The results of DFT calculations, at the PCM/ωB97x-D/def2-TZVPD level of theory, are in good agreement with the experiments. The transition states of the SN2 intramolecular cyclization of vicinal haloamines have been modeled.

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Section: Resultsmentioning

confidence: 99%

Access to 2-Fluorinated Aziridine-2-phosphonates from α,α-Halofluorinated β-Iminophosphonates—Spectroscopic and Theoretical Studies

et al. 2023

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“…Several years later, Koroniak and co‐workers reported that a similar preparation of β‐amino‐α,α‐dilfuorophosphonates could not be achieved because the preparation of imines by condensation of difluorinated oxo substrates with amines was unsuccessful, which prompted them to explore fluorination of β‐iminophosphonates 171 as shown in Scheme 60 [212] . Iminophosphonates 171 reacted more readily than the analogous oxo phosphonates mentioned above – presumably because the intermediate enamines are more nucleophilic than enolates – and only 2 equivalents of Selectfluor were required to achieve moderate to good yields of difluorinated imines 172 .…”

Section: Synthetic Methodsmentioning

confidence: 99%

Recent Advances in Synthesis of Difluoromethylene Phosphonates for Biological Applications

et al. 2021

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For almost 40 years, difluoromethylene phosphonates have proven to be versatile molecular tools in biochemical studies owing to their close resemblance to naturally occurring phosphates and phosphonates. As bioisosteric, non‐hydrolyzable analogs of these essential molecules, difluoromethylene phosphonates can target the critical parts of the cellular machinery and therefore exhibit a diverse spectrum of biological activity. In the past ten years, there have appeared many new methods for the synthesis of difluoromethylene phosphonates. Most notably, photoredox catalysis has firmly entered the field, while cross‐coupling and nucleophilic strategies have met considerable elaboration and refinement, entirely in accord with the current trends in synthetic organic chemistry. Herein, we introduce difluoromethylene phosphonates as a distinct, high‐tech subclass of synthetic phosphonates resulting from the research efforts on the cross‐section of organophosphorus, organofluorine, and bioorganic chemistry. We then proceed to the discussion of general methods for the preparation of difluoromethylene phosphonates, comprehensively reviewing reactions developed in the past 15 years while providing the context of earlier works where appropriate. Finally, we present selected examples of molecules with high biological activity, their biological targets, and the synthetic steps employed for their preparation.

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“…Secondary b-enaminophosphonates derived from b-keto phosphonates were subjected to the fluorination by Selectfluor at reflux of acetonitrile to yield the gem-difluorinated iminophosphonates (Eq. 39)[77]. From the pyrrolidine-based enamine, the electrophilic fluorination conducted at -10 C gave the corresponding a-fluoro-b-ketophosphonate in 55% yield (Eq.…”

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Selectfluor and Its Analogs Electrophilic Fluorination for Preparing Alkyl Fluorides

Guyon¹,

Cahard²

2017

Fluorination

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Synthesis and spectral properties of α,α-difluorinated β-iminophosphonates

Cited by 7 publications

References 34 publications

Access to 2-Fluorinated Aziridine-2-phosphonates from α,α-Halofluorinated β-Iminophosphonates—Spectroscopic and Theoretical Studies

Access to 2-Fluorinated Aziridine-2-phosphonates from α,α-Halofluorinated β-Iminophosphonates—Spectroscopic and Theoretical Studies

Recent Advances in Synthesis of Difluoromethylene Phosphonates for Biological Applications

Selectfluor and Its Analogs Electrophilic Fluorination for Preparing Alkyl Fluorides

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