A Novel Synthesis of 1-Aminoalkanephosphonic Acid Derivatives from 1-(<i>N</i>-Acylamino)- alkyltriphenylphosphonium Salts

Mazurkiewicz, Roman; Październiok-Holewa, Agnieszka; Kononienko, Alicja

doi:10.1080/10426500903436735

Cited by 13 publications

(8 citation statements)

References 10 publications

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“…Recently we developed a simple and effective two-step transformation of N -acyl-α-amino acids into their phosphonic analogues that allows for easy access to a variety of structurally diversified N -acyl-α-aminophosphonates 5 (Scheme 1) [36–37]. …”

Section: Resultsmentioning

confidence: 99%

A new method for the synthesis of α-aminoalkylidenebisphosphonates and their asymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogues

Kuźnik¹,

Mazurkiewicz²,

Grymel³

et al. 2015

Beilstein J. Org. Chem.

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SummaryA convenient approach has been developed to α-aminoalkylidenebisphosphonates and their asymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogues by α-phosphonylation, α-phosphinylation or α-phosphinoylation of 1-(N-acylamino)alkylphosphonates, that, in turn, are easily accessible from N-acyl-α-amino acids. Effective electrophilic activation of the α-position of 1-(N-acetylamino)alkylphosphonates was achieved by electrochemical α-methoxylation of these compounds in methanol, mediated with NaCl, followed by displacement of the methoxy group with triphenylphosphonium tetrafluoroborate to give hitherto unknown 1-(N-acetylamino)-1-triphenylphosphoniumalkylphosphonate tetrafluoroborates. The latter compounds react smoothly with trialkyl phosphites, dialkyl phosphonites or alkyl phosphinites in the presence of Hünig’s base and methyltriphenylphosphonium iodide in a Michaelis–Arbuzov-like reaction to give the expected alkylidenebisphosphonates, 1-phosphinylalkylphosphonates or 1-phosphinoylalkylphosphonates, respectively, in good yields.

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Section: Resultsmentioning

confidence: 99%

A new method for the synthesis of α-aminoalkylidenebisphosphonates and their asymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogues

Kuźnik¹,

Mazurkiewicz²,

Grymel³

et al. 2015

Beilstein J. Org. Chem.

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“…A base (e.g., the Hünig’s base-( i -Pr) 2 EtN) facilitates the cleavage of the C α -P + bond and the formation of corresponding N -acylimine. In turn, the iodide anion (introduced as methyltriphenylphosphonium iodide) enables dealkylation of the intermediate alkoxyphosphonium salt 36 ( Scheme 11 ) [ 50 , 51 , 52 ]. Further studies showed that the reaction could be carried out also under a catalytic-free conditions [ 46 , 52 ].…”

Section: 1-aminoalkyltriarylphosphonium Derivativesmentioning

confidence: 99%

1-Aminoalkylphosphonium Derivatives: Smart Synthetic Equivalents of N-Acyliminium-Type Cations, and Maybe Something More: A Review

et al. 2022

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N-acyliminium-type cations are examples of highly reactive intermediates that are willingly used in organic synthesis in intra- or intermolecular α-amidoalkylation reactions. They are usually generated in situ from their corresponding precursors in the presence of acidic catalysts (Brønsted or Lewis acids). In this context, 1-aminoalkyltriarylphosphonium derivatives deserve particular attention. The positively charged phosphonium moiety located in the immediate vicinity of the N-acyl group significantly facilitates Cα-P+ bond breaking, even without the use of catalyst. Moreover, minor structural modifications of 1-aminoalkyltriarylphosphonium derivatives make it possible to modulate their reactivity in a simple way. Therefore, these types of compounds can be considered as smart synthetic equivalents of N-acyliminium-type cations. This review intends to familiarize a wide audience with the unique properties of 1-aminoalkyltriarylphosphonium derivatives and encourage their wider use in organic synthesis. Hence, the most important methods for the preparation of 1-aminoalkyltriarylphosphonium salts, as well as the area of their potential synthetic utilization, are demonstrated. In particular, the structure–reactivity correlations for the phosphonium salts are discussed. It was shown that 1-aminoalkyltriarylphosphonium salts are not only an interesting alternative to other α-amidoalkylating agents but also can be used in such important transformations as the Wittig reaction or heterocyclizations. Finally, the prospects and limitations of their further applications in synthesis and medicinal chemistry were considered.

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“…Other substrates that have been used in this reaction in the presence of Hünig’s base and methyltriphenylphosphonium iodide as catalysts are diethyl 1-( N -acetylamino)-1-triphenylphosphoniumalkylphosphonate tetrafluoroborates 4 , which can be considered as α-functionalized triphenylphosphonium derivatives of 1-( N -acylamino)alkylphosphonates [ 30 ]. The starting phosphonium salts 4 were synthesized here from diethyl 1-aminoalkylphosphonates readily available from N -acyl-α-amino acids [ 31 , 32 ] by initially subjecting them to electrochemical oxidation to introduce the nucleofugal methoxy group into the α-position, which was followed by nucleophilic substitution of the obtained diethyl 1-( N -acetylamino)-1-methoxyalkylphosphonates with triphenylphosphonium tetrafluoroborate ( Scheme 1 , pathway a). The biggest limitation of this transformation is the electrochemical oxidation step, which was efficiently performed for only two of the simplest models of phosphorus analogs of α-amino acids, namely for the derivative of glycine and alanine, having at the α-position a hydrogen atom or a methyl group, respectively.…”

Section: Introductionmentioning

confidence: 99%

One-Pot and Catalyst-Free Transformation of N-Protected 1-Amino-1-Ethoxyalkylphosphonates into Bisphosphonic Analogs of Protein and Non-Protein α-Amino Acids

et al. 2022

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Herein, we describe the development of one-pot transformation of α-ethoxy derivatives of phosphorus analogs of protein and non-protein α-amino acids into biologically important N-protected 1-aminobisphosphonates. The proposed strategy, based on the three-component reaction of 1-(N-acylamino)-1-ethoxyphosphonates with triphenylphosphonium tetrafluoroborate and triethyl phosphite, facilitates good to excellent yields under mild reaction conditions. The course of the reaction was monitored by 31P NMR spectroscopy, allowing the identification of probable intermediate species, thus making it possible to propose a reaction mechanism. In most cases, there is no need to use a catalyst to provide transformation efficiency, which increases its attractiveness both in economic and ecological terms. Furthermore, we demonstrate that the one-pot procedure can be successfully applied for the synthesis of structurally diverse N-protected bisphosphonic analogs of α-amino acids. As shown, the indirect formation of the corresponding phosphonium salt as a reactive intermediate during the conversion of 1-(N-acylamino)-1-ethoxyphosphonate into a 1-aminobisphosphonate derivative is a crucial component of the developed methodology.

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A Novel Synthesis of 1-Aminoalkanephosphonic Acid Derivatives from 1-(N-Acylamino)- alkyltriphenylphosphonium Salts

Cited by 13 publications

References 10 publications

A new method for the synthesis of α-aminoalkylidenebisphosphonates and their asymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogues

A new method for the synthesis of α-aminoalkylidenebisphosphonates and their asymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogues

1-Aminoalkylphosphonium Derivatives: Smart Synthetic Equivalents of N-Acyliminium-Type Cations, and Maybe Something More: A Review

One-Pot and Catalyst-Free Transformation of N-Protected 1-Amino-1-Ethoxyalkylphosphonates into Bisphosphonic Analogs of Protein and Non-Protein α-Amino Acids

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