Catalytic sp3-sp3 Functionalisation of Sulfonamides: Late-Stage Modification of Drug-Like Molecules

Othman Abdulla, Adam D. Clayton, Robert A. Faulkner, Duncan M. Gill, Craig R. Rice, Scarlett M. Walton, Joseph B. Sweeney

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

A new application of Pd-catalysed allylation is reported that enables the synthesis of a range of branched sp3-functionalised sulfonamides, a compound class for which few reported methods exist. By reacting benzyl sulfonamides with allylic acetates in the presence of Pd0 catalysts and base at room temperature, direct allylation was efficiently performed, yielding products that are analogues of structural motifs seen in biologically active small molecules. The reaction was performed under mild conditions and could be applied to nanomolar sigma-receptor binders, thus enabling a late-stage functionalisation and efficient expansion of drug-like chemical space.
LanguageEnglish
Pages1494-1497
Number of pages4
JournalChemistry - A European Journal
Volume23
Issue number7
Early online date18 Jan 2017
DOIs
Publication statusPublished - 31 Jan 2017

Fingerprint

Allylation
Sulfonamides
sigma Receptors
Molecules
Pharmaceutical Preparations
Binders
Acetates
Catalysts
Temperature

Cite this

Abdulla, Othman ; Clayton, Adam D. ; Faulkner, Robert A. ; Gill, Duncan M. ; Rice, Craig R. ; Walton, Scarlett M. ; Sweeney, Joseph B. / Catalytic sp3-sp3 Functionalisation of Sulfonamides : Late-Stage Modification of Drug-Like Molecules. In: Chemistry - A European Journal. 2017 ; Vol. 23, No. 7. pp. 1494-1497.
@article{bd0249e3a2e84402856d1186900ddf8b,
title = "Catalytic sp3-sp3 Functionalisation of Sulfonamides: Late-Stage Modification of Drug-Like Molecules",
abstract = "A new application of Pd-catalysed allylation is reported that enables the synthesis of a range of branched sp3-functionalised sulfonamides, a compound class for which few reported methods exist. By reacting benzyl sulfonamides with allylic acetates in the presence of Pd0 catalysts and base at room temperature, direct allylation was efficiently performed, yielding products that are analogues of structural motifs seen in biologically active small molecules. The reaction was performed under mild conditions and could be applied to nanomolar sigma-receptor binders, thus enabling a late-stage functionalisation and efficient expansion of drug-like chemical space.",
keywords = "Catalysis, Late-stage functionalisation, Palladium, Sigma receptor, Sulfonamides",
author = "Othman Abdulla and Clayton, {Adam D.} and Faulkner, {Robert A.} and Gill, {Duncan M.} and Rice, {Craig R.} and Walton, {Scarlett M.} and Sweeney, {Joseph B.}",
note = "Not OA compliant; no full text on Eprints SH 13/9/17.",
year = "2017",
month = "1",
day = "31",
doi = "10.1002/chem.201605464",
language = "English",
volume = "23",
pages = "1494--1497",
journal = "Chemistry - A European Journal",
issn = "0947-6539",
publisher = "Wiley-VCH Verlag",
number = "7",

}

Catalytic sp3-sp3 Functionalisation of Sulfonamides : Late-Stage Modification of Drug-Like Molecules. / Abdulla, Othman; Clayton, Adam D.; Faulkner, Robert A.; Gill, Duncan M.; Rice, Craig R.; Walton, Scarlett M.; Sweeney, Joseph B.

In: Chemistry - A European Journal, Vol. 23, No. 7, 31.01.2017, p. 1494-1497.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Catalytic sp3-sp3 Functionalisation of Sulfonamides

T2 - Chemistry - A European Journal

AU - Abdulla, Othman

AU - Clayton, Adam D.

AU - Faulkner, Robert A.

AU - Gill, Duncan M.

AU - Rice, Craig R.

AU - Walton, Scarlett M.

AU - Sweeney, Joseph B.

N1 - Not OA compliant; no full text on Eprints SH 13/9/17.

PY - 2017/1/31

Y1 - 2017/1/31

N2 - A new application of Pd-catalysed allylation is reported that enables the synthesis of a range of branched sp3-functionalised sulfonamides, a compound class for which few reported methods exist. By reacting benzyl sulfonamides with allylic acetates in the presence of Pd0 catalysts and base at room temperature, direct allylation was efficiently performed, yielding products that are analogues of structural motifs seen in biologically active small molecules. The reaction was performed under mild conditions and could be applied to nanomolar sigma-receptor binders, thus enabling a late-stage functionalisation and efficient expansion of drug-like chemical space.

AB - A new application of Pd-catalysed allylation is reported that enables the synthesis of a range of branched sp3-functionalised sulfonamides, a compound class for which few reported methods exist. By reacting benzyl sulfonamides with allylic acetates in the presence of Pd0 catalysts and base at room temperature, direct allylation was efficiently performed, yielding products that are analogues of structural motifs seen in biologically active small molecules. The reaction was performed under mild conditions and could be applied to nanomolar sigma-receptor binders, thus enabling a late-stage functionalisation and efficient expansion of drug-like chemical space.

KW - Catalysis

KW - Late-stage functionalisation

KW - Palladium

KW - Sigma receptor

KW - Sulfonamides

U2 - 10.1002/chem.201605464

DO - 10.1002/chem.201605464

M3 - Article

VL - 23

SP - 1494

EP - 1497

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

SN - 0947-6539

IS - 7

ER -