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Development of a Method for the N-Arylation of Amino Acid Esters with Aryl Triflates

[Image: see text] A general method for the N-arylation of amino acid esters with aryl triflates is described. Both α- and β-amino acid esters, including methyl, tert-butyl, and benzyl esters, are viable substrates. Reaction optimization was carried out by design of experiment (DOE) analysis using JM...

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Autores principales: King, Sandra M., Buchwald, Stephen L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2016
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010016/
https://www.ncbi.nlm.nih.gov/pubmed/27498618
http://dx.doi.org/10.1021/acs.orglett.6b02082
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author King, Sandra M.
Buchwald, Stephen L.
author_facet King, Sandra M.
Buchwald, Stephen L.
author_sort King, Sandra M.
collection PubMed
description [Image: see text] A general method for the N-arylation of amino acid esters with aryl triflates is described. Both α- and β-amino acid esters, including methyl, tert-butyl, and benzyl esters, are viable substrates. Reaction optimization was carried out by design of experiment (DOE) analysis using JMP software. The mild reaction conditions, which use t-BuBrettPhos Pd G3 or G4 precatalyst, result in minimal racemization of the amino acid ester. This method is the first synthetic application of the t-BuBrettPhos Pd G4 precatalyst. Mechanistic studies show that the observed erosion in enantiomeric excess is due to racemization of the amino acid ester starting material and not of the product.
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spelling pubmed-50100162017-08-08 Development of a Method for the N-Arylation of Amino Acid Esters with Aryl Triflates King, Sandra M. Buchwald, Stephen L. Org Lett [Image: see text] A general method for the N-arylation of amino acid esters with aryl triflates is described. Both α- and β-amino acid esters, including methyl, tert-butyl, and benzyl esters, are viable substrates. Reaction optimization was carried out by design of experiment (DOE) analysis using JMP software. The mild reaction conditions, which use t-BuBrettPhos Pd G3 or G4 precatalyst, result in minimal racemization of the amino acid ester. This method is the first synthetic application of the t-BuBrettPhos Pd G4 precatalyst. Mechanistic studies show that the observed erosion in enantiomeric excess is due to racemization of the amino acid ester starting material and not of the product. American Chemical Society 2016-08-08 2016-08-19 /pmc/articles/PMC5010016/ /pubmed/27498618 http://dx.doi.org/10.1021/acs.orglett.6b02082 Text en Copyright © 2016 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle King, Sandra M.
Buchwald, Stephen L.
Development of a Method for the N-Arylation of Amino Acid Esters with Aryl Triflates
title Development of a Method for the N-Arylation of Amino Acid Esters with Aryl Triflates
title_full Development of a Method for the N-Arylation of Amino Acid Esters with Aryl Triflates
title_fullStr Development of a Method for the N-Arylation of Amino Acid Esters with Aryl Triflates
title_full_unstemmed Development of a Method for the N-Arylation of Amino Acid Esters with Aryl Triflates
title_short Development of a Method for the N-Arylation of Amino Acid Esters with Aryl Triflates
title_sort development of a method for the n-arylation of amino acid esters with aryl triflates
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010016/
https://www.ncbi.nlm.nih.gov/pubmed/27498618
http://dx.doi.org/10.1021/acs.orglett.6b02082
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