title: Catalytic sp3-sp3Functionalisation 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 Pd0catalysts 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.
authors.affiliation: Department of Chemical Sciences, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK.
authors.forename: Othman
authors.initials: O
authors.lastname: Abdulla
authors.affiliation: Department of Chemical Sciences, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Clayton
authors.affiliation: Department of Chemical Sciences, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Faulkner
authors.affiliation: Department of Chemical Sciences, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK.
authors.forename: Duncan M
authors.initials: DM
authors.lastname: Gill
authors.affiliation: Department of Chemical Sciences, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Rice
authors.affiliation: Department of Chemical Sciences, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK.
authors.forename: Scarlett M
authors.initials: SM
authors.lastname: Walton
authors.affiliation: Department of Chemical Sciences, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK.
authors.forename: Joseph B
authors.identifier: http://orcid.org/0000-0001-7593-9598
authors.initials: JB
authors.lastname: Sweeney
mesh_terms: D000085:Acetates / Q000737:chemistry; D000498:Allyl Compounds / Q000737:chemistry; D002384:Catalysis; D010165:Palladium; D011789:Quantum Theory; D013449:Sulfonamides / Q000737:chemistry*; D013696:Temperature
chemical_list: D000085:Acetates; D000498:Allyl Compounds; D013449:Sulfonamides; D010165:Palladium; C498551:allyl acetate
keywords: catalysis; late-stage functionalisation; palladium; sigma receptor; sulfonamides