Generation of Acyl Anion Equivalents from Acylphosphonates via Phosphonate−Phosphate Rearrangement:  A Highly Practical Method for Cross-Benzoin Reaction

As, Demir; Reis, Ömer; Ac, Iğdir; I, Esiringü; Eymür, Serkan

doi:10.1021/jo051811u

Cited by 79 publications

(18 citation statements)

References 17 publications

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“…These products can be used for the generation of valuable acyl anion equivalents via phosphonate-phosphate rearrangement. 8 As a general extension of this work, we are currently investigating the asymmetric version of this reaction as well as addition reactions with TMS derivatives other than TMSCN.…”

Section: Methodsmentioning

confidence: 99%

“…Acylphosphonate (1 mmol 8,15.2,(d,J = 5.7 Hz),15.4,(d,J = 5.8 Hz), 63.6 (d, J = 6.9 Hz), 64.2 (d,J = 7.6 Hz),70.4. 116.1,127.1,127.2,127.2,127.5,132.2,134.6.…”

Section: General Procedures For Tmscn Additionmentioning

confidence: 99%

“…8 During our investigations regarding the nature of carbanionic intermediates that are generated via phosphonate-phosphate rearrangement we needed to synthesize compound 2a (Scheme 1). In an initial reaction, acylphosphonate 1a was dissolved in 1 mL toluene, and 1.2 mmol (1.2 equiv) of TMSCN was slowly added via a syringe.…”

mentioning

confidence: 99%

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Uncatalyzed Addition of TMSCN to Acylphosphonates

Demir¹,

Reis²,

Kayalar³

et al. 2006

Synlett

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The cyanosilylations of various alkyl-and arylphosphonates under comparatively mild conditions furnished the trimethylsilyloxycyanophosphonates in high yield. The addition to ketophosphonate functions works without the influence of a catalyst.The addition of trimethylsilyl cyanide (TMSCN) to carbonyl compounds along with the subsequent hydrolysis in turn produces cyanohydrins. 1 Cyanohydrins are useful intermediates for the synthesis of many interesting compounds with biological properties. The two functional groups (-OH and -CN) can be easily transformed into various compounds. 2 The general route to O-TMS cyanohydrins is the addition of TMSCN to the aldehydes (or ketones), which only occurs in the presence of Lewis acid 3a and nucleophilic catalysis. 3b,c When considering the value of O-TMS cyanohydrins, it is not surprising that catalysis was reported hundreds of times so far for this particular transformation, and continue to be reported at the same pace. 4Phosphorus analogues of hydroxycarboxylic acids as well as phosphorylated a-hydroxynitriles are interesting as potential biologically active substances, mild water-soluble phosphorylating agents for biological systems, and watersoluble ligands for metal complex catalysis. Only a few methods have been described for the addition of carbon nucleophiles to acylphosphonates, 5 and as far as we know, only two methods describe the synthesis of phosphorylated a-hydroxynitriles. Konovalova et al. 6 obtained these compounds by the reaction of trimethylsilyl diethyl phosphite with esters and nitriles of a-oxocarboxylic acids. Beletskaya 7 reported the reaction of a-, b-, and g-ketophosphonates with TMSCN to only occur with catalytic Bu 3 SnCN at elevated temperatures (50-60°C, 6-8 h) and acetylphosphonate was only example for a-ketophosphonate. In this present paper, we investigated the scope of the addition reaction of TMSCN to ketophosphonate for the synthesis of a-trimethylsilyloxynitrile, which are interesting precursors in synthetic organic chemistry, in which we found that TMSCN adds to ketophosphonate in high yield without any influence from a catalyst.In our previous work we have shown that acylphosphonates are potent acyl anion precursors and that they undergo nucleophile-promoted phosphonate-phosphate rearrangement in order to provide corresponding acyl anion equivalents as reactive intermediates. 8 During our investigations regarding the nature of carbanionic intermediates that are generated via phosphonate-phosphate rearrangement we needed to synthesize compound 2a (Scheme 1). In an initial reaction, acylphosphonate 1a was dissolved in 1 mL toluene, and 1.2 mmol (1.2 equiv) of TMSCN was slowly added via a syringe. After the completion of the reaction (15-30 min), a reaction mixture was concentrated under vacuum and purified by column chromatography (ether eluent) to obtain 2a in 98% yield. Scheme 1After rapid screening with 1a and 1b, we found that the reaction indeed proceeds smoothly in various solvents. For example, we observed similar purities in DMF,...

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Section: Methodsmentioning

confidence: 99%

“…Acylphosphonate (1 mmol 8,15.2,(d,J = 5.7 Hz),15.4,(d,J = 5.8 Hz), 63.6 (d, J = 6.9 Hz), 64.2 (d,J = 7.6 Hz),70.4. 116.1,127.1,127.2,127.2,127.5,132.2,134.6.…”

Section: General Procedures For Tmscn Additionmentioning

confidence: 99%

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Uncatalyzed Addition of TMSCN to Acylphosphonates

Demir¹,

Reis²,

Kayalar³

et al. 2006

Synlett

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“…[2] Although significant progress has been made with enantioselective and intramolecular versions in recent years, [3] there still are limitations in the intermolecular coupling of two different aldehydes and of aldehydes with ketones. In these cases the outcome is typically a mixture of all possible symmetrical and unsymmetrical acyloins, with the chemoselectivity strongly depending on the relative thermodynamic stability of the corresponding products.[4] In order to overcome this problem several research groups have made excellent contributions by developing enzymatic approaches [5] or utilizing acylsilanes [6] and acylphosphonates [7] as acyl anion equivalents in cyanide-catalyzed transformations. In addition, very recently Scheidt et al reported intermolecular cross-acyloin reactions by fluoride-promoted addition of O-silylthiazolium salts.…”

mentioning

confidence: 99%

A Direct Intermolecular Cross‐Benzoin Type Reaction: N‐Heterocyclic Carbene‐Catalyzed Coupling of Aromatic Aldehydes with Trifluoromethyl Ketones

Enders

Henseler

2009

Adv Synth Catal

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A direct intermolecular cross-benzointype condensation catalyzed by an N-heterocyclic carbene has been developed. The cross-coupling of commercially available aromatic aldehydes and trifluoromethyl ketones results in a-hydroxy-a-trifluoromethyl ketones bearing a quaternary stereocenter with excellent chemoselectivity and good to excellent yields.Keywords: cross-benzoin reaction; N-heterocyclic carbenes; organocatalysis; trifluoromethyl substitution; umpolungIn their pioneering and historic paper on the benzoyl compounds of 1832 [1] Wçhler and Liebig not only started the chemistry of aromatic compounds, such as benzaldehyde, benzoic acid, benzoyl chloride and benzamide, but also reported the cyanide-catalyzed (bitter almond oil) formation of benzoin, which in a sense can be seen as the start of organocatalysis. Since these early days of organic chemistry, the cyanide-and later carbene-catalyzed coupling of two aldehyde molecules to form the corresponding a-hydroxy ketones (benzoin, acyloin) has been investigated extensively. [2] Although significant progress has been made with enantioselective and intramolecular versions in recent years, [3] there still are limitations in the intermolecular coupling of two different aldehydes and of aldehydes with ketones. In these cases the outcome is typically a mixture of all possible symmetrical and unsymmetrical acyloins, with the chemoselectivity strongly depending on the relative thermodynamic stability of the corresponding products.[4] In order to overcome this problem several research groups have made excellent contributions by developing enzymatic approaches [5] or utilizing acylsilanes [6] and acylphosphonates [7] as acyl anion equivalents in cyanide-catalyzed transformations. In addition, very recently Scheidt et al. reported intermolecular cross-acyloin reactions by fluoride-promoted addition of O-silylthiazolium salts.[8] However, to the best of our knowledge, there is no precedent for a direct organocatalytic intermolecular coupling of aldehydes with ketones, which we would like to report in this communication.Based on our mechanistic proposal for the Stetter reaction, which relies on a reversible formation of the benzoin product prior to the Stetter product formation, [9] we envisaged to use benzoins as masked aldehyde equivalents.[10] To our delight, benzoin (1) in combination with an excess of trifluoroacetophenone (2) as reactive electrophilic ketone component led chemoselectively to the crossed acyloin product 3 in high yield, employing 20 mol% of the bicyclic triazolium salt 4[11] as precatalyst in the presence of 20 mol% DBU in THF at room temperature (Scheme 1).Since the crossed acyloin product 3 containing a tertiary alcohol seemed to be energetically preferred relative to benzoin (1) a simpler and more practical version of this concept would be to employ the aldehyde component directly in this transformation (Scheme 2). Under the reaction conditions given (10 mol% carbene precursor 4 and 10 mol% DBU), it was indeed possible to obtain the cross-co...

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“…(3)]. [13] Furthermore, the strong basic catalysts potentially excluded the hydrophosphonylation of base-sensitive ketones, even mild bases such as tertiary amines may also cause side reactions.…”

Section: Highly Efficient Synthesis Of Quaternary A-hydroxymentioning

confidence: 99%

Highly Efficient Synthesis of Quaternary α‐Hydroxy Phosphonates via Lewis Acid‐Catalyzed Hydrophosphonylation of Ketones

et al. 2009

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A Lewis acid catalyst has been first applied to the hydrophosphonylation of ketones, giving the corresponding quaternary a-hydroxy phosphonates in high yields (up to 98%). The present method was highly tolerable for functionalized ketones. Moreover, the first catalytic enantioselective hydrophosphonylation of an unactivated ketone was also realized by using a tridentate Schiff base-titanium complex.

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Generation of Acyl Anion Equivalents from Acylphosphonates via Phosphonate−Phosphate Rearrangement: A Highly Practical Method for Cross-Benzoin Reaction

Cited by 79 publications

References 17 publications

Uncatalyzed Addition of TMSCN to Acylphosphonates

Uncatalyzed Addition of TMSCN to Acylphosphonates

A Direct Intermolecular Cross‐Benzoin Type Reaction: N‐Heterocyclic Carbene‐Catalyzed Coupling of Aromatic Aldehydes with Trifluoromethyl Ketones

Highly Efficient Synthesis of Quaternary α‐Hydroxy Phosphonates via Lewis Acid‐Catalyzed Hydrophosphonylation of Ketones

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