Enantioselective synthesis of β-fluoro-β-aryl-α-amino pentenamides by organocatalytic [2,3]-sigmatropic rearrangement

Kevin Kasten; Alexandra M. Z. Slawin; Andrew D. Smith

doi:10.1021/acs.orglett.7b02452

Enantioselective synthesis of β-fluoro-β-aryl-α-amino pentenamides by organocatalytic [2,3]-sigmatropic rearrangement

Kevin Kasten, Alexandra M. Z. Slawin, Andrew D. Smith^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

The tetramisole-promoted catalytic enantioselective [2,3]-sigmatropic rearrangement of quaternary ammonium salts bearing a (Z)-3-fluoro-3-arylprop-2-ene group generates, after addition of benzylamine, a range of β-fluoro-β-aryl-α-aminopentenamides containing a stereogenic tertiary fluorine substituent. Cyclic and acyclic nitrogen substituents as well as various aromatic substituents are tolerated, giving the β-fluoro-β-aryl-α-aminopentenamide products in up to 76% yield, 96:4 dr, and 98:2 er.

Original language	English
Pages (from-to)	5182-5185
Number of pages	4
Journal	Organic Letters
Volume	19
Issue number	19
Early online date	8 Sept 2017
DOIs	https://doi.org/10.1021/acs.orglett.7b02452
Publication status	Published - 6 Oct 2017

Keywords

Flluorinated amino-acids
Allylic ammonium ylides
Kinetic resolution
Medicinal chemistry
Protein design
Catalysts
Mannich
Benzotetramisole
Straightforward
Cycloaddition

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10.1021/acs.orglett.7b02452

Smith_2017_OrgLetters_Enantioselectve_AAM
Copyright © 2017 American Chemical Society. This work has been made available online in accordance with the publisher’s policies. This is the author created accepted version manuscript following peer review and as such may differ slightly from the final published version. The final published version of this work is available at: https://doi.org/10.1021/acs.orglett.7b02452
Accepted author manuscript, 754 KB

Cite this

@article{07670065865e41af9c626aebd918224a,

title = "Enantioselective synthesis of β-fluoro-β-aryl-α-amino pentenamides by organocatalytic [2,3]-sigmatropic rearrangement",

abstract = "The tetramisole-promoted catalytic enantioselective [2,3]-sigmatropic rearrangement of quaternary ammonium salts bearing a (Z)-3-fluoro-3-arylprop-2-ene group generates, after addition of benzylamine, a range of β-fluoro-β-aryl-α-aminopentenamides containing a stereogenic tertiary fluorine substituent. Cyclic and acyclic nitrogen substituents as well as various aromatic substituents are tolerated, giving the β-fluoro-β-aryl-α-aminopentenamide products in up to 76% yield, 96:4 dr, and 98:2 er.",

keywords = "Flluorinated amino-acids, Allylic ammonium ylides, Kinetic resolution, Medicinal chemistry, Protein design, Catalysts, Mannich, Benzotetramisole, Straightforward, Cycloaddition",

author = "Kevin Kasten and Slawin, {Alexandra M. Z.} and Smith, {Andrew D.}",

note = "The research leading to these results (K.K.) has received funding from the ERC under the European Union's Seventh Framework Programme (FP7/2007-2013) / ERC grant agreement n° 279850. A.D.S. thanks the Royal Society for a Wolfson Research Merit Award.",

year = "2017",

month = oct,

day = "6",

doi = "10.1021/acs.orglett.7b02452",

language = "English",

volume = "19",

pages = "5182--5185",

journal = "Organic Letters",

issn = "1523-7060",

publisher = "American Chemical Society (ACS)",

number = "19",

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T1 - Enantioselective synthesis of β-fluoro-β-aryl-α-amino pentenamides by organocatalytic [2,3]-sigmatropic rearrangement

AU - Kasten, Kevin

AU - Slawin, Alexandra M. Z.

AU - Smith, Andrew D.

N1 - The research leading to these results (K.K.) has received funding from the ERC under the European Union's Seventh Framework Programme (FP7/2007-2013) / ERC grant agreement n° 279850. A.D.S. thanks the Royal Society for a Wolfson Research Merit Award.

PY - 2017/10/6

Y1 - 2017/10/6

N2 - The tetramisole-promoted catalytic enantioselective [2,3]-sigmatropic rearrangement of quaternary ammonium salts bearing a (Z)-3-fluoro-3-arylprop-2-ene group generates, after addition of benzylamine, a range of β-fluoro-β-aryl-α-aminopentenamides containing a stereogenic tertiary fluorine substituent. Cyclic and acyclic nitrogen substituents as well as various aromatic substituents are tolerated, giving the β-fluoro-β-aryl-α-aminopentenamide products in up to 76% yield, 96:4 dr, and 98:2 er.

AB - The tetramisole-promoted catalytic enantioselective [2,3]-sigmatropic rearrangement of quaternary ammonium salts bearing a (Z)-3-fluoro-3-arylprop-2-ene group generates, after addition of benzylamine, a range of β-fluoro-β-aryl-α-aminopentenamides containing a stereogenic tertiary fluorine substituent. Cyclic and acyclic nitrogen substituents as well as various aromatic substituents are tolerated, giving the β-fluoro-β-aryl-α-aminopentenamide products in up to 76% yield, 96:4 dr, and 98:2 er.

KW - Flluorinated amino-acids

KW - Allylic ammonium ylides

KW - Kinetic resolution

KW - Medicinal chemistry

KW - Protein design

KW - Catalysts

KW - Mannich

KW - Benzotetramisole

KW - Straightforward

KW - Cycloaddition

UR - http://pubs.acs.org/doi/suppl/10.1021/acs.orglett.7b02452

U2 - 10.1021/acs.orglett.7b02452

DO - 10.1021/acs.orglett.7b02452

M3 - Article

SN - 1523-7060

VL - 19

SP - 5182

EP - 5185

JO - Organic Letters

JF - Organic Letters

IS - 19

ER -

Enantioselective synthesis of β-fluoro-β-aryl-α-amino pentenamides by organocatalytic [2,3]-sigmatropic rearrangement

Abstract

Keywords

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RS Wolfson Merit Award: Developing Catalysis Research: New Reaction Discoveries and Practical Applications

ERC Starting Grant EnolCat: Emulating nature: Reaction diversity and understanding through asymmetric catalysis

data underpinning "Enantioselective synthesis of tertiary β-fluoro-β-aryl-α-amino amides by organocatalytic [2,3]-sigmatropic rearrangement

Cite this

Enantioselective synthesis of β-fluoro-β-aryl-α-amino pentenamides by organocatalytic [2,3]-sigmatropic rearrangement

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Projects

RS Wolfson Merit Award: Developing Catalysis Research: New Reaction Discoveries and Practical Applications

ERC Starting Grant EnolCat: Emulating nature: Reaction diversity and understanding through asymmetric catalysis

Datasets

data underpinning "Enantioselective synthesis of tertiary β-fluoro-β-aryl-α-amino amides by organocatalytic [2,3]-sigmatropic rearrangement

Cite this