Exploring the scope of tandem palladium and isothiourea relay catalysis for the synthesis of α-amino acid derivatives

Jacqueline Bitai; Alexandra M. Z. Slawin; David B. Cordes; Andrew D. Smith

doi:10.3390/molecules25102463

Exploring the scope of tandem palladium and isothiourea relay catalysis for the synthesis of α-amino acid derivatives

Jacqueline Bitai, Alexandra M. Z. Slawin, David B. Cordes, Andrew D. Smith

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

6 Citations (Scopus)

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Abstract

The scope and limitations of a tandem N-allylation/[2,3]-rearrangementprotocol are investigated through the incorporation of a variety of functionalgroups within an allylic phosphate precursor. This method uses readilyaccessible N,N-dimethylglycine aryl esters and functionalizedallylic phosphates, forming quaternary ammonium salts in situ in the presence of a palladium catalyst. Subsequentenantioselective [2,3]-sigmatropic rearrangement, promoted by the chiralisothiourea tetramisole, generates α-amino acid derivatives with two contiguousstereocenters. The incorporation of electron withdrawing ester and amide groupsgave the best results, furnishing the desired products in moderate to goodyields (29-70%), with low diastereocontrol (typically 60:40 dr) but highenantioselectivity (up to 90:10 er). These results indicate that substrate-catalystinteractions in the proposed transition state are sensitive to the substitutionpattern of the substrates.

Original language	English
Article number	2463
Number of pages	13
Journal	Molecules
Volume	25
Issue number	10
DOIs	https://doi.org/10.3390/molecules25102463
Publication status	Published - 25 May 2020

Keywords

Isothiourea
Palladium
Enantioselective catalysis
Amino acids
[2,3]-rearrangement
N-allylation

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10.3390/molecules25102463Licence: CC BY

Bitai_2020_Molecules_Tandem_CC
Copyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Final published version, 6.78 MBLicence: CC BY

RS Wolfson Merit Award: Developing Catalysis Research: New Reaction Discoveries and Practical Applications
Smith, A. D. (PI)
The Royal Society
1/01/15 → 31/12/19
Project: Fellowship

Exploring the Scope of Tandem Palladium and Isothiourea Relay Catalysis for the Synthesis of α-Amino Acid Derivatives (dataset)
Smith, A. D. (Creator) & Bitai, J. (Owner), University of St Andrews, 22 May 2020
DOI: 10.17630/1991da1b-e4f2-4a3c-8364-271023c723e2
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title = "Exploring the scope of tandem palladium and isothiourea relay catalysis for the synthesis of α-amino acid derivatives",

abstract = "The scope and limitations of a tandem N-allylation/[2,3]-rearrangementprotocol are investigated through the incorporation of a variety of functionalgroups within an allylic phosphate precursor. This method uses readilyaccessible N,N-dimethylglycine aryl esters and functionalizedallylic phosphates, forming quaternary ammonium salts in situ in the presence of a palladium catalyst. Subsequentenantioselective [2,3]-sigmatropic rearrangement, promoted by the chiralisothiourea tetramisole, generates α-amino acid derivatives with two contiguousstereocenters. The incorporation of electron withdrawing ester and amide groupsgave the best results, furnishing the desired products in moderate to goodyields (29-70%), with low diastereocontrol (typically 60:40 dr) but highenantioselectivity (up to 90:10 er). These results indicate that substrate-catalystinteractions in the proposed transition state are sensitive to the substitutionpattern of the substrates. ",

keywords = "Isothiourea, Palladium, Enantioselective catalysis, Amino acids, [2,3]-rearrangement, N-allylation",

author = "Jacqueline Bitai and Slawin, {Alexandra M. Z.} and Cordes, {David B.} and Smith, {Andrew D.}",

note = "Funding: This research was funded by the School of Chemistry, University of St Andrews. A.D.S. thanks the Royal Society for a Wolfson Research Merit Award.",

year = "2020",

month = may,

day = "25",

doi = "10.3390/molecules25102463",

language = "English",

volume = "25",

journal = "Molecules",

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TY - JOUR

T1 - Exploring the scope of tandem palladium and isothiourea relay catalysis for the synthesis of α-amino acid derivatives

AU - Bitai, Jacqueline

AU - Slawin, Alexandra M. Z.

AU - Cordes, David B.

AU - Smith, Andrew D.

N1 - Funding: This research was funded by the School of Chemistry, University of St Andrews. A.D.S. thanks the Royal Society for a Wolfson Research Merit Award.

PY - 2020/5/25

Y1 - 2020/5/25

N2 - The scope and limitations of a tandem N-allylation/[2,3]-rearrangementprotocol are investigated through the incorporation of a variety of functionalgroups within an allylic phosphate precursor. This method uses readilyaccessible N,N-dimethylglycine aryl esters and functionalizedallylic phosphates, forming quaternary ammonium salts in situ in the presence of a palladium catalyst. Subsequentenantioselective [2,3]-sigmatropic rearrangement, promoted by the chiralisothiourea tetramisole, generates α-amino acid derivatives with two contiguousstereocenters. The incorporation of electron withdrawing ester and amide groupsgave the best results, furnishing the desired products in moderate to goodyields (29-70%), with low diastereocontrol (typically 60:40 dr) but highenantioselectivity (up to 90:10 er). These results indicate that substrate-catalystinteractions in the proposed transition state are sensitive to the substitutionpattern of the substrates.

AB - The scope and limitations of a tandem N-allylation/[2,3]-rearrangementprotocol are investigated through the incorporation of a variety of functionalgroups within an allylic phosphate precursor. This method uses readilyaccessible N,N-dimethylglycine aryl esters and functionalizedallylic phosphates, forming quaternary ammonium salts in situ in the presence of a palladium catalyst. Subsequentenantioselective [2,3]-sigmatropic rearrangement, promoted by the chiralisothiourea tetramisole, generates α-amino acid derivatives with two contiguousstereocenters. The incorporation of electron withdrawing ester and amide groupsgave the best results, furnishing the desired products in moderate to goodyields (29-70%), with low diastereocontrol (typically 60:40 dr) but highenantioselectivity (up to 90:10 er). These results indicate that substrate-catalystinteractions in the proposed transition state are sensitive to the substitutionpattern of the substrates.

KW - Isothiourea

KW - Palladium

KW - Enantioselective catalysis

KW - Amino acids

KW - [2,3]-rearrangement

KW - N-allylation

U2 - 10.3390/molecules25102463

DO - 10.3390/molecules25102463

M3 - Article

SN - 1420-3049

VL - 25

JO - Molecules

JF - Molecules

IS - 10

M1 - 2463

ER -

Exploring the scope of tandem palladium and isothiourea relay catalysis for the synthesis of α-amino acid derivatives

Abstract

Keywords

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Projects

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

Datasets

Exploring the Scope of Tandem Palladium and Isothiourea Relay Catalysis for the Synthesis of α-Amino Acid Derivatives (dataset)

Cite this