One‐Pot Tandem 1,4–1,2‐Addition of Phosphites to α,β‐Unsaturated Imines for the Synthesis of Glutamic Acid Analogues

Moonen, Kristof; Meenen, Ellen Van; Verwée, Annelies; Stevens, Christian V.

doi:10.1002/anie.200501830

Cited by 46 publications

(44 citation statements)

References 28 publications

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“…Using dialkyl trimethylsilyl phosphite, the highly steric t-Bu group is the best N-substituent to obtain double adducts, while phenyl, a less sterically hindered nitrogen substituent, resulted only in the 1,2-adducts. 27 As was the case for the dialkyl trimethylsilyl phosphite tandem addition, 27 the acid also plays a crucial role in the trialkyl phosphite addition. Next to the imine activation and enamine tautomerization, the acid (or its conjugated base) is required for dealkylation of the phosphonium intermediates (see below).…”

Section: Methodsmentioning

confidence: 97%

On the discovery and development of tandem 1,4- and 1,2-addition of phosphites to 1-azadienes

Waes¹,

Debrouwer²,

Heugebaert³

et al. 2014

Arkivoc

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Over the past 15 years we have developed a one-step protocol for the synthesis of 3-phosphonylated aminophosphonates from α,β-unsaturated imines through tandem 1,4-1,2-phosphite addition. This account covers the initial development, mechanistic implications of using different phosphite nucleophiles and the expansion towards oximes, hydrazones and unsaturated imines included in aromatic sextets, e.g. quinolines, phenanthrolines and napthyridines.

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Section: Methodsmentioning

confidence: 97%

On the discovery and development of tandem 1,4- and 1,2-addition of phosphites to 1-azadienes

Waes¹,

Debrouwer²,

Heugebaert³

et al. 2014

Arkivoc

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“…[40] Surprisingly, the reaction was very efficient when using sulfuric acid as the catalyst. This result prompted us to replace triethylammonium chloride by sulfuric acid.…”

Section: Synthesis Of the α-Phosphonic Analogue Of Aminocitratementioning

confidence: 99%

“…After extraction with CH 2 Cl 2 , the aqueous phase was concentrated under vacuum, and the residue was dried under high vacuum to furnish 7 as a white solid (40 …”

Section: -Amino-3-phosphonopentane-15-dioic Acid Hydrochloride (7)mentioning

confidence: 99%

Aminophosphonic Acids and Aminobis(phosphonic acids) as Potential Inhibitors of Penicillin‐Binding Proteins

et al. 2008

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Aminophosphonic acids and aminobis(phosphonic acids) have been prepared by the alkylation of Schiff bases with methyl bromoacetate or ethyl acrylate. Other pathways, like the modified Pudovik reaction and Kabachnik–Fields reaction, have been considered for the synthesis of the α‐phosphonic bioisoster of aminocitrate. Partial or complete deprotection of the phosphonate ester have been realised by either acidic hydrolysis or by treatment with trimethylsilyl bromide. Evaluation against penicillin‐binding proteins has shown that our compounds are modest inhibitors of class A β‐lactamases, but have an interesting activity against R39 (D,D‐peptidase/carboxypeptidase). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

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“…4,5 Hydrazones 2 (derived from hydrazines or hydrazides) are, despite the lower reactivity in comparison to imines, appropriate substrates for the synthesis of 3-phosphonyl-1-hydrazinophosphonates 3 in one step. prepared in a separate reaction.…”

Section: Scheme 1 Synthesis Of 3-phosphonyl-1-hydrazinophosphonatesmentioning

confidence: 99%

One-Pot Tandem 1,4- and 1,2-Addition of Phosphites to α,β-Unsaturated Hydrazones

Stevens¹,

Meenen²,

Masschelein³

et al. 2007

Synlett

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The 1,4-and 1,2-addition of phosphites to a,b-unsaturated hydrazones was investigated. When silylated phosphites and trialkyl phosphites were compared, trialkyl phosphites gave better conversions and subsequently higher yields. A variety of hydrazones were evaluated as substrate in this reaction, which yield 3-phosphonyl-1-hydrazinoalkyl phosphonates.a-Hydrazinoalkyl phosphonic acids 1 ( Figure 1) and their derivatives have been found to have an interesting protecting effect against the phytotoxic action of chloroacetanilide herbicides. 1 Limited research was performed to establish a general route to this type of compounds. 2 Among the specific methods, the lithium perchlorate/diethyl ether catalyzed multicomponent reaction of an aldehyde, a hydrazine, and silylated phosphite 2e or the binary reagent (MeO) 3 P/Me 3 SiCl 2f seems to be the most straightforward. However, this method is only applicable to aliphatic aldehydes. Figure 1 a-Hydrazinoalkyl phosphonic acidAs a continuation of our studies on the behavior of different phosphorus nucleophiles and the chemistry of azaheterocyclic phosphonates, 3 the addition of silylated phosphites and trialkyl phosphites to a,b-unsaturated hydrazones 2 is presented in this paper (Scheme 1). In this reaction, two phosphonate moieties are introduced in one single reaction to form 3-phosphonyl-1-hydrazinoalkyl phosphonates 3. Our previous research showed that both reagents are able to perform a tandem 1,4-1,2-addition to a,b-unsaturated imines. 4,5 A mechanistic study proved a different reactivity of both phosphorus reagents. Trialkyl phosphites show a higher tendency to perform 1,4-addition than 1,2-addition, where a reverse reactivity is noticed with silylated phosphites. To evaluate the scope of these reactions, hydrazones 2, which were anticipated to be much less reactive compared to imines, have now been evaluated as possible substrates. Scheme 1 Synthesis of 3-phosphonyl-1-hydrazinophosphonates 3To synthesize the substrates 2, an a,b-unsaturated aldehyde was dissolved in methanol in the presence of one equivalent of the hydrazine or hydrazide. After one hour at 0°C, the solvent was evaporated in vacuo and the products were recovered in excellent yields (95-99%).The first part of the research comprised the evaluation of silylated phosphite as a phosphorus nucleophile and was based on the work of Afarinkia and co-workers for the synthesis of a-aminophosphonates. 6 O-Silylation of dialkyl phosphite provided the more nucleophilic s 3 l 3 reagent. 7 In these experiments the hydrazone 2 was dissolved in dry dichloromethane, and 5 equivalents of silylated phosphite were added. This mixture was heated to reflux temperature after which 0.5 equivalents of sulfuric acid were added.Follow-up of the reaction by 31 P NMR (whenever possible, conversions were calculated from integrations in the 31 P NMR) had shown a very slow and incomplete conversion. 8 Imines, on the other hand, showed vigorous reaction upon addition of sulfuric acid (the solvent starts to boil) and the reactions were ...

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One‐Pot Tandem 1,4–1,2‐Addition of Phosphites to α,β‐Unsaturated Imines for the Synthesis of Glutamic Acid Analogues

Cited by 46 publications

References 28 publications

On the discovery and development of tandem 1,4- and 1,2-addition of phosphites to 1-azadienes

On the discovery and development of tandem 1,4- and 1,2-addition of phosphites to 1-azadienes

Aminophosphonic Acids and Aminobis(phosphonic acids) as Potential Inhibitors of Penicillin‐Binding Proteins

One-Pot Tandem 1,4- and 1,2-Addition of Phosphites to α,β-Unsaturated Hydrazones

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