Synthesis of (S) 2-ethyl-2-methylpentanoic acid from the formate ester of (S) ethyl 2-formyl-3-hydroxy-2-methylpropionate

Fronza, Giovanni; Fogliato, Giovanni; Fuganti, Claudio; Grasselli, Piero; Rigoni, Romina

doi:10.1016/0040-4020(96)00880-0

“…Although this direct hydrolysis was not practical, it did allow the stereochemistry of the alkylation process to be elucidated. Comparison of the optical rotation of 4 with literature data established that the S isomer was formed in the alkylation step 25. Thus, the alkylation occurs from the top face of the enolate [as drawn in Eq.…”

Section: Methodsmentioning

confidence: 88%

Stereoselective Formation of Quaternary Carbon Centers: Alkylation ofα,α-Disubstituted Amide Enolates

Manthorpe

¹

,

Gleason

²

2002

Angew. Chem. Int. Ed.

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The stereoselective formation of quaternary carbon centers is one of the most challenging tasks in organic chemistry and can only be achieved using methods which employ some form of carbon ± carbon bond forming reaction. [1] One of the most straightforward methods for the formation of carbon ± carbon bonds is the alkylation of an enolate with an alkyl halide and, fluoride ions were 1 to 2 mm. The protonation constant of fluoride in water is: log K HF/F 3.15. NMR Measurements: 1 H NMR spectra were recorded on a Bruker AM500 spectrometer at 500 MHz. Binding constants were obtained by NMR titrations of L with fluoride from 25 measurements in D 2 O at pD 5.0 AE 0.1. Initial concentrations were [L] 0 2 mm and titrations were performed using aliquots from a 20 mm stock solution of NaF. A solution of the sodium salt of [2,2,3,3-D 4 ]-3-(trimethylsilyl)propionic acid (TPS) in D 2 O in a capillary tube was used as an external reference. The pD value was adjusted with a concentrated solution of TsOH and NaOD in D 2 O. All spectra were recorded at room temperature. The association constants K s were calculated by fitting f to d obs (consisting of several independent NMR signals) with a 1:1 association model using Sigma Plot software. Equations (1) and (2) were used, where L is the ligand and A À is the anion, and the error limit in K is less than 10 %:The Job×s plot was performed by examining different concentration ratios of L and NaF in D 2 O at pD 5.0 AE 0.1, while maintaining the total concentration of the ligand plus NaF at 10 mm. The pD value was adjusted with a concentrated solution of TsOH and NaOD in D 2 O. NMR measurements were recorded at room temperature.

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“…For instance, reaction of enolate 2 a with ethyl iodide instead of allyl bromide afforded the corresponding product 3 c with 96.5:3.5 diastereoselectivity (93 % de). [25] Thus, the alkylation occurs from the top face of the enolate [as drawn in Eq. The yields were high and in most cases the reactions proceeded to completion within 4 h at À 78 8C without added polar co-solvents.…”

mentioning

confidence: 99%

Stereoselective Formation of Quaternary Carbon Centers: Alkylation ofα,α-Disubstituted Amide Enolates

Manthorpe

¹

,

Gleason

²

2002

Angew. Chem.

15

0

View full text Add to dashboard Cite

The stereoselective formation of quaternary carbon centers is one of the most challenging tasks in organic chemistry and can only be achieved using methods which employ some form of carbon ± carbon bond forming reaction. [1] One of the most straightforward methods for the formation of carbon ± carbon bonds is the alkylation of an enolate with an alkyl halide and, fluoride ions were 1 to 2 mm. The protonation constant of fluoride in water is: log K HF/F 3.15. NMR Measurements: 1 H NMR spectra were recorded on a Bruker AM500 spectrometer at 500 MHz. Binding constants were obtained by NMR titrations of L with fluoride from 25 measurements in D 2 O at pD 5.0 AE 0.1. Initial concentrations were [L] 0 2 mm and titrations were performed using aliquots from a 20 mm stock solution of NaF. A solution of the sodium salt of [2,2,3,3-D 4 ]-3-(trimethylsilyl)propionic acid (TPS) in D 2 O in a capillary tube was used as an external reference. The pD value was adjusted with a concentrated solution of TsOH and NaOD in D 2 O. All spectra were recorded at room temperature. The association constants K s were calculated by fitting f to d obs (consisting of several independent NMR signals) with a 1:1 association model using Sigma Plot software. Equations (1) and (2) were used, where L is the ligand and A À is the anion, and the error limit in K is less than 10 %:The Job×s plot was performed by examining different concentration ratios of L and NaF in D 2 O at pD 5.0 AE 0.1, while maintaining the total concentration of the ligand plus NaF at 10 mm. The pD value was adjusted with a concentrated solution of TsOH and NaOD in D 2 O. NMR measurements were recorded at room temperature.

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ChemInform Abstract: Synthesis of (S)‐2‐Ethyl‐2‐methylpentanoic Acid from the Formate Ester of (S) Ethyl 2‐Formyl‐3‐hydroxy‐2‐methylpropionate.

Fronza¹,

Fogliato²,

Fuganti³

et al. 1997

ChemInform

0

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Synthesis of (S) 2-ethyl-2-methylpentanoic acid from the formate ester of (S) ethyl 2-formyl-3-hydroxy-2-methylpropionate

Cited by 5 publications

References 11 publications

Stereoselective Formation of Quaternary Carbon Centers: Alkylation ofα,α-Disubstituted Amide Enolates

Stereoselective Formation of Quaternary Carbon Centers: Alkylation ofα,α-Disubstituted Amide Enolates

Stereoselective Formation of Quaternary Carbon Centers: Alkylation ofα,α-Disubstituted Amide Enolates

ChemInform Abstract: Synthesis of (S)‐2‐Ethyl‐2‐methylpentanoic Acid from the Formate Ester of (S) Ethyl 2‐Formyl‐3‐hydroxy‐2‐methylpropionate.

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