(E)-Selective Horner–Wadsworth–Emmons reaction of aryl alkyl ketones with bis(2,2,2-trifluoroethyl)phosphonoacetic acid

Sano, Shigeki; Takemoto, Yuka; Nagao, Yoshimitsu

doi:10.1016/j.tetlet.2003.09.185

Cited by 15 publications

(4 citation statements)

References 24 publications

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“…15,16) That is to say, the phosphonate moiety of 1 was found to be more easily hydrolyzed than the ester moiety of 1 under aqueous alkaline conditions. Thus, the phosphonoacetic acid was readily prepared by enzymatic hydrolysis of 1 with porcine liver esterase (PLE).…”

Section: )mentioning

confidence: 99%

A Facile Synthesis of Novel Chiral Phosphonoacetates Bearing a Stereogenic Phosphorus Atom

Sano

Kujime

Takemoto

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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Asymmetric Horner-Wadsworth-Emmons (HWE) reaction of prochiral cyclic ketones is of current interest.1-4) Several useful chiral HWE reagents such as phosphonates, [5][6][7][8][9] phosphonoamides, 10) and phosphonoamidates 11) have been developed for the synthesis of olefins possessing an axis of chirality. However, most of these reagents are restricted to the compounds with non-stereogenic phosphorus atom. Although Motoyoshiya et al. reported geometrical selectivity of HWE reactions of aldehydes with racemic phosphonoacetates, 12) the asymmetric HWE reaction of P-stereogenic phosphonoacetates has never been established. Herein we describe a facile synthesis of novel chiral phosphonoacetates bearing a stereogenic phosphorus atom utilizing the enzymecatalyzed kinetic resolution of racemic phosphonoacetates derived from two kinds of Z-selective HWE reagents, methyl bis(2,2,2-trifluoroehtyl)phosphonoacetate (Still's reagent, 1)13) and ethyl diphenylphosphonoacetate (2). 14)Recently, we reported a new and efficient stereoselective HWE reaction of aldehydes and ketones with bis(2,2,2-trifluoroehtyl)phosphonoacetic acid and found oxophilicity of a phosphorus atom of phosphonoacetate 1. 15,16) That is to say, the phosphonate moiety of 1 was found to be more easily hydrolyzed than the ester moiety of 1 under aqueous alkaline conditions. Thus, the phosphonoacetic acid was readily prepared by enzymatic hydrolysis of 1 with porcine liver esterase (PLE). Although attempts to hydrolyze the ester moiety of 1 under aqueous alkaline conditions were unsuccessful, reactions of 1 with various alcohols in the presence of triethylamine or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) gave the corresponding phosphonoacetate rac-3a-d as the major product (Chart 1). The similar transformation of 2 using various alcohols gave rac-4a-d as shown in Chart 2. Attempts to hydrolyze 2 under aqueous alkaline conditions were also unsuccessful, though phosphonoacetates 4a and 5-7 were obtained (Chart 2). It can be concluded that the high oxophilicity of phosphorus atoms of these HWE reagents 1 and 2 appears to be necessary for Z-selective HWE reaction with aldehydes. [17][18][19] The phosphonoacetates rac-3a-d were subjected to enzymatic hydrolysis utilizing PLE (Sigma, E-2884), as follows. Phosphonoacetates rac-3a-d were dissolved in 1/15 M phosphate buffer solution (pH 7.4) and acetone (9 : 1). After addition of PLE (800 units/mmol), the mixture was stirred at room temperature for the appropriate time. The reaction mixture was treated with 10% HCl and then extracted with AcOEt. After evaporation of the extraction in vacuo, the residue was purified on a silica gel column with CHCl 3 -MeOH as eluent to give the corresponding carboxylic acid 8 and unreacted ester 3. The enantiomeric excess of resolution product 8 was determined by means of HPLC analysis with chiral-stationary-phase (CSP) after methylation with (trimethylsilyl)diazomethane (TMSCHN 2 ). 20) Unreacted resolution compound 3 was also subjected to HPLC analysis with CSP. As the result of enz...

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Section: )mentioning

confidence: 99%

A Facile Synthesis of Novel Chiral Phosphonoacetates Bearing a Stereogenic Phosphorus Atom

Sano

Kujime

Takemoto

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…17 The stereochemistry of the C=C double bond of the disubstituted a,b-unsaturated amide was assigned on the basis of the value of the 1 H NMR coupling constant between the olefinic protons. 18 As temperature can affect the selectivity in these reactions, 19 we performed several control experiments for the reaction of the phosphonamide 2 with isobutyraldehyde and isovaleraldehyde. The results are summarized in Table 2.…”

Section: Scheme 1 Preparation Of Phosphonamides 2 Andmentioning

confidence: 99%

Practical and Efficient Synthesis of (E)-α,β-Unsaturated Amides Bearing (S)-α-Methylbenzylamine from 2-Phosphonamides via Horner-Wadsworth-Emmons Reaction

Hernández-Fernández¹,

Fernández‐Zertuche²,

García-Barradas³

et al. 2006

Synlett

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E ) -a , b -U n s a t u r a t e d A m i d e s B e a r i n g ( S ) -a -M e t h y l b e n z y l a m i n e Abstract: The highly stereoselective synthesis of (E)-a,b-unsaturated amides bearing (S)-a-methylbenzylamine was achieved from 2-phosphonamides via Horner-Wadsworth-Emmons reaction. The starting phosphonamides are easily prepared in two steps with excellent yields via the standard Arbuzov reaction of trimethylphosphite and a-bromoamides.

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“…In the first step, nucleophilic substitution of the 1st alcohol 2 at the phosphorus center of methyl bis(2,2,2-trifluoroethyl)phosphonoacetate (StillGennari reagent, 1) 28,29 furnishes the common key intermediate The reaction of the Still-Gennari reagent (1) and chiral alcohol 2 was conducted in the presence of a 1 equiv of DBU and molecular sieves (type 3A) based on our previous report. 30,31 As a result, mixed phosphonoacetate 3 was obtained as an inseparable diastereomeric mixture (ca. 1:1) in 82% yield (Scheme 4).…”

Section: Introductionmentioning

confidence: 99%

A novel synthetic approach to glycerophospholipids via Horner–Wadsworth–Emmons reaction of mixed phosphonoacetate

Sano

Sumiyoshi

Handa

et al. 2015

Tetrahedron Letters

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(E)-Selective Horner–Wadsworth–Emmons reaction of aryl alkyl ketones with bis(2,2,2-trifluoroethyl)phosphonoacetic acid

Cited by 15 publications

References 24 publications

A Facile Synthesis of Novel Chiral Phosphonoacetates Bearing a Stereogenic Phosphorus Atom

A Facile Synthesis of Novel Chiral Phosphonoacetates Bearing a Stereogenic Phosphorus Atom

Practical and Efficient Synthesis of (E)-α,β-Unsaturated Amides Bearing (S)-α-Methylbenzylamine from 2-Phosphonamides via Horner-Wadsworth-Emmons Reaction

A novel synthetic approach to glycerophospholipids via Horner–Wadsworth–Emmons reaction of mixed phosphonoacetate

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