Catalyst-free Mannich-type reaction of 1-(N-acylamino)alkyltriphenylphosphonium salts with silyl enolates

Październiok-Holewa, Agnieszka; Walęcka-Kurczyk, Alicja; Musioł, Szymon; Stecko, Sebastian

doi:10.1016/j.tet.2018.12.042

Cited by 9 publications

(6 citation statements)

References 71 publications

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“…The presence of an acylamino group next to a positively charged phosphonium moiety permits the use of N -protected 1-aminoalkylphosphonium salts as very effective α-amidoalkylating agents (i.e., precursors of N -acylimines or N -acyliminium cations) in the α-amidoalkylation reaction. It has been demonstrated that under appropriate conditions, N -protected 1-aminoalkylphosphonium salts readily react with both carbon- and heteronucleophiles, leading to the formation of new C–C and C–heteroatom bonds, respectively. − Moreover, the reactivity of these salts can be improved by imposing some structural modifications, especially within the phosphonium group. The introduction of electron-withdrawing substituents (e.g., Cl, CF 3 ) into the phosphonium moiety weakens the C α –P + bond, thereby facilitating its cleavage and promoting the generation of iminium-type cations, which are the proper α-amidoalkylating agents.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of N-Protected 1-Aminoalkylphosphonium Salts from Amides, Carbamates, Lactams, or Imides

2021

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This report describes the development and optimization of the one-pot method for the synthesis of N -protected 1-aminoalkylphosphonium salts based on the three-component coupling of aldehydes and either amides, carbamates, lactams, imides, or urea in the presence of triarylphosphonium salts. The proposed strategy is very efficient and easy to carry out even on a larger scale (20 g) in any typical laboratory. Most reactions occur at temperatures between 50 and 100 °C in a short time (1–2 h) without requiring any catalyst, and simple workup procedures afford good to excellent yields. The exceptions are condensations with imides, which require much higher temperatures (150–170 °C) and longer reaction times (even 30 h). The possibility of carrying out the synthesis under solvent-free conditions (neat reactions) is also demonstrated. It is especially important for less reactive substrates (imides), and reactions required high temperature (or generally harsher conditions). Finally, we prove the developed one-pot methodology can be successfully applied for the synthesis of structurally diverse N -protected 1-aminoalkylphosphonium salts. Mechanistic studies showed the intermediate products of described couplings are 1-hydroxyalkylphosphonium salts, not N -hydroxyalkylamides, -imides, etc., as initially expected.

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Section: Introductionmentioning

confidence: 99%

Synthesis of N-Protected 1-Aminoalkylphosphonium Salts from Amides, Carbamates, Lactams, or Imides

2021

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“…Among the examined catalysts, 4-F-substituted catalyst 4, derived from hydroquinine, and 2-methoxy substituted catalyst 5, derived from quinine, gave the best results (see Table 1, entries 2 and 5). Taking into account the strong amidoalkylating properties of phosphonium salts 2 [40,41], we decided to perform the next Here, we present our recent results on the enantioselective catalytic α-amidoalkylation of dimethyl phosphite with 1-(N-acylamino)alkylphosphonium salts 2 in the presence of a chiral catalyst. Taking into account that the starting 1-(N-acylamino)alkylphosphonium tetrafluoroborates 2 are readily available from N-acyl-α-amino acids 1, the presented approach can be considered a new strategy for the transformation of N-acyl-α-amino acids 1 into non-racemic 1-(N-acylamino)alkylphosphonic acid esters 3 (Scheme 2b).…”

Section: Results S and Discussionmentioning

confidence: 99%

“…The starting phosphonium salts 2a-k were synthesized by a previously described two-step protocol [25], which consists of electrochemical decarboxylative α-methoxylation of N-acyl-α-amino acids (Step 1) and transformation of the resulting N-(1-methoxyalkyl)carbamates to 1-(N-acylamino)alkyltriphenylphosphonium tetrafluoroborates 2 (Step 2). The analytical data and spectra of compounds 2a-f,j,k were identical to those previously described [25,41]. For previously unknown phosphonium salts 2g-i, analytical and spectroscopic data are reported below.…”

Section: Substrate Synthesismentioning

confidence: 99%

The Synthesis of α-Aminophosphonates via Enantioselective Organocatalytic Reaction of 1-(N-Acylamino)alkylphosphonium Salts with Dimethyl Phosphite

et al. 2020

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α-Aminophosphonic acids are phosphorus analogues of α-amino acids. Compounds of this type find numerous applications in medicine and crop protection due to their unique biological activities. A crucial factor in these activities is the configuration of the stereoisomers. Only a few methods of stereoselective transformation of α-amino acids into their phosphorus analogues are known so far and all of them are based on asymmetric induction, thus involving the use of a chiral substrate. In contrast, we have focused our efforts on the development of an effective method for this type of transformation using a racemic mixture of starting N-protected α-amino acids and a chiral catalyst. Herein, a simple and efficient stereoselective organocatalytic α-amidoalkylation of dimethyl phosphite by 1-(N-acylamino)alkyltriphenylphosphonium salts to enantiomerically enriched α-aminophosphonates is reported. Using 5 mol% of chiral quinine- or hydroquinine-derived quaternary ammonium salts provides final products in very good yields up to 98% and with up to 92% ee. The starting phosphonium salts were easily obtained from α-amino acid derivatives by decarboxylative methoxylation and subsequent substitution with triphenylphosphonium tetrafluoroborate. The appropriate self-disproportionation of enantiomers (SDE) test for selected α-aminophosphonate derivatives via achiral flash chromatography was performed to confirm the reliability of the enantioselectivity results that were obtained.

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“…As Październiok-Holewa et al demonstrated, the process can be carried out in THF at 50 °C or 60 °C using conventional heating or microwave irradiation. The proposed mechanism of the transformation included, in the first stage, the formation of the reactive N -acyliminium cation 3 , which further reacts with the silyl enolate to give silyloxy-substituted carbenium ion 70 , which fast undergoes a desilylation reaction to give β-amino carbonyl compounds 68 or 69 ( Scheme 18 /B) [ 64 ].…”

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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Catalyst-free Mannich-type reaction of 1-(N-acylamino)alkyltriphenylphosphonium salts with silyl enolates

Cited by 9 publications

References 71 publications

Synthesis of N-Protected 1-Aminoalkylphosphonium Salts from Amides, Carbamates, Lactams, or Imides

Synthesis of N-Protected 1-Aminoalkylphosphonium Salts from Amides, Carbamates, Lactams, or Imides

The Synthesis of α-Aminophosphonates via Enantioselective Organocatalytic Reaction of 1-(N-Acylamino)alkylphosphonium Salts with Dimethyl Phosphite

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

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