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Chiral fluoroacetic acid: synthesis of (R)- and (S)-[H-2(1)]-fluoroacetate in high enantiopurity

Research output: Contribution to journalArticlepeer-review

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Chiral fluoroacetic acid: synthesis of (R)- and (S)-[H-2(1)]-fluoroacetate in high enantiopurity. / Wadoux, Rudy D. P.; Lin, Xiaowei; Keddie, Neil S.; O'Hagan, David.

In: Tetrahedron: Asymmetry, Vol. 24, No. 12, 30.06.2013, p. 719-723.

Research output: Contribution to journalArticlepeer-review

Harvard

Wadoux, RDP, Lin, X, Keddie, NS & O'Hagan, D 2013, 'Chiral fluoroacetic acid: synthesis of (R)- and (S)-[H-2(1)]-fluoroacetate in high enantiopurity', Tetrahedron: Asymmetry, vol. 24, no. 12, pp. 719-723. https://doi.org/10.1016/j.tetasy.2013.05.001

APA

Wadoux, R. D. P., Lin, X., Keddie, N. S., & O'Hagan, D. (2013). Chiral fluoroacetic acid: synthesis of (R)- and (S)-[H-2(1)]-fluoroacetate in high enantiopurity. Tetrahedron: Asymmetry, 24(12), 719-723. https://doi.org/10.1016/j.tetasy.2013.05.001

Vancouver

Wadoux RDP, Lin X, Keddie NS, O'Hagan D. Chiral fluoroacetic acid: synthesis of (R)- and (S)-[H-2(1)]-fluoroacetate in high enantiopurity. Tetrahedron: Asymmetry. 2013 Jun 30;24(12):719-723. https://doi.org/10.1016/j.tetasy.2013.05.001

Author

Wadoux, Rudy D. P. ; Lin, Xiaowei ; Keddie, Neil S. ; O'Hagan, David. / Chiral fluoroacetic acid: synthesis of (R)- and (S)-[H-2(1)]-fluoroacetate in high enantiopurity. In: Tetrahedron: Asymmetry. 2013 ; Vol. 24, No. 12. pp. 719-723.

Bibtex - Download

@article{c13e62308cd54a93a04e8f29400ae63f,
title = "Chiral fluoroacetic acid: synthesis of (R)- and (S)-[H-2(1)]-fluoroacetate in high enantiopurity",
abstract = "A two-step synthesis of (R)- and (S)-[H-2(1)]-fluoroacetate (sodium salts) in high enantioselectivity is reported. The synthesis is the development of a previous one in which the enantioselectivity has been increased from similar to 38% ee to >95% ee. The improvement in enantioselectivity applied Bio's methodology, which involved a deoxyfluorination reaction with DAST on either enantiomer of [H-2(1)]-benzyl alcohol, adding TMS-morpholine to the reaction. The additive promotes an S(N)2 inversion process, and suppresses a competing non-stereospecific S(N)1 reaction course, and as a result significantly improves the stereointegrity of the C-F bond formation. The intermediate [H-2(1)]-benzyl alcohols, [H-2(1)]-benzyl fluorides and the product [H-2(1)]-fluoroacetates as their hexyl esters were separately assayed for their stereochemical integrity, using the Courtieu method. This method involved measuring their H-2 NMR spectra in a chiral matrix of poly-gamma-benzyl L-glutamate. The chiral assay demonstrated that there was no significant loss in stereointegrity during the deoxyfluorination reaction and showed that the enantiomers of [H-2(1)]-fluoroacetate were generated with high enantiomeric purity (95% ee). (C) 2013 Elsevier Ltd. All rights reserved.",
keywords = "DEUTERIUM NMR, STREPTOMYCES CATTLEYA, ENANTIOMERIC ANALYSIS, FLUORINATION",
author = "Wadoux, {Rudy D. P.} and Xiaowei Lin and Keddie, {Neil S.} and David O'Hagan",
note = "The authors thank the ERC for an Advanced Investigator Award to DO{\textquoteright}H and we thank the EPSRC for a research Grant (EPSRC GR/EP/HO22651/1) to support this work.",
year = "2013",
month = jun,
day = "30",
doi = "10.1016/j.tetasy.2013.05.001",
language = "English",
volume = "24",
pages = "719--723",
journal = "Tetrahedron: Asymmetry",
issn = "0957-4166",
publisher = "Elsevier",
number = "12",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Chiral fluoroacetic acid: synthesis of (R)- and (S)-[H-2(1)]-fluoroacetate in high enantiopurity

AU - Wadoux, Rudy D. P.

AU - Lin, Xiaowei

AU - Keddie, Neil S.

AU - O'Hagan, David

N1 - The authors thank the ERC for an Advanced Investigator Award to DO’H and we thank the EPSRC for a research Grant (EPSRC GR/EP/HO22651/1) to support this work.

PY - 2013/6/30

Y1 - 2013/6/30

N2 - A two-step synthesis of (R)- and (S)-[H-2(1)]-fluoroacetate (sodium salts) in high enantioselectivity is reported. The synthesis is the development of a previous one in which the enantioselectivity has been increased from similar to 38% ee to >95% ee. The improvement in enantioselectivity applied Bio's methodology, which involved a deoxyfluorination reaction with DAST on either enantiomer of [H-2(1)]-benzyl alcohol, adding TMS-morpholine to the reaction. The additive promotes an S(N)2 inversion process, and suppresses a competing non-stereospecific S(N)1 reaction course, and as a result significantly improves the stereointegrity of the C-F bond formation. The intermediate [H-2(1)]-benzyl alcohols, [H-2(1)]-benzyl fluorides and the product [H-2(1)]-fluoroacetates as their hexyl esters were separately assayed for their stereochemical integrity, using the Courtieu method. This method involved measuring their H-2 NMR spectra in a chiral matrix of poly-gamma-benzyl L-glutamate. The chiral assay demonstrated that there was no significant loss in stereointegrity during the deoxyfluorination reaction and showed that the enantiomers of [H-2(1)]-fluoroacetate were generated with high enantiomeric purity (95% ee). (C) 2013 Elsevier Ltd. All rights reserved.

AB - A two-step synthesis of (R)- and (S)-[H-2(1)]-fluoroacetate (sodium salts) in high enantioselectivity is reported. The synthesis is the development of a previous one in which the enantioselectivity has been increased from similar to 38% ee to >95% ee. The improvement in enantioselectivity applied Bio's methodology, which involved a deoxyfluorination reaction with DAST on either enantiomer of [H-2(1)]-benzyl alcohol, adding TMS-morpholine to the reaction. The additive promotes an S(N)2 inversion process, and suppresses a competing non-stereospecific S(N)1 reaction course, and as a result significantly improves the stereointegrity of the C-F bond formation. The intermediate [H-2(1)]-benzyl alcohols, [H-2(1)]-benzyl fluorides and the product [H-2(1)]-fluoroacetates as their hexyl esters were separately assayed for their stereochemical integrity, using the Courtieu method. This method involved measuring their H-2 NMR spectra in a chiral matrix of poly-gamma-benzyl L-glutamate. The chiral assay demonstrated that there was no significant loss in stereointegrity during the deoxyfluorination reaction and showed that the enantiomers of [H-2(1)]-fluoroacetate were generated with high enantiomeric purity (95% ee). (C) 2013 Elsevier Ltd. All rights reserved.

KW - DEUTERIUM NMR

KW - STREPTOMYCES CATTLEYA

KW - ENANTIOMERIC ANALYSIS

KW - FLUORINATION

U2 - 10.1016/j.tetasy.2013.05.001

DO - 10.1016/j.tetasy.2013.05.001

M3 - Article

VL - 24

SP - 719

EP - 723

JO - Tetrahedron: Asymmetry

JF - Tetrahedron: Asymmetry

SN - 0957-4166

IS - 12

ER -

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