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 sp -functionalised sulfonamides, a compound class for which few reported methods exist. By reacting benzyl sulfonamides with allylic acetates in the presence of Pd 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.

Deliberately Losing Control of C−H Activation Processes in the Design of Small‐Molecule‐Fragment Arrays Targeting Peroxisomal Metabolism

“…[1] Highly decorated bioactive or synthetically relevant molecules can be functionalised in a late-stage activation process, enabling the efficient production of derivatives for, for example, structure activity studies or pharmacokinetic evaluation, saving significant time and cost compared to previous cumbersome multistep syntheses. [2][3][4][5][6][7][8][9][10][11][12][13][14] We have recently disclosed our findings on the microwave mediated ortho-CÀ H activation of benzodiazepines using iodonium salts under Pd catalysis ( Figure 1). [15] These processes tend to give monoarylated products although, under more forcing conditions, a second ortho-arylation was observed.…”

Late-stage functionalization of 5-nitrofurans derivatives and their antibacterial activities

“…C-H late-stage functionalization (LSF) is the most direct approach of structural modication, helping to generate new drugs rapidly. [8][9][10][11][12][13] So far, there have been many examples of successfully improving activity aer modication such as "magic methyl" effect, [14][15][16][17][18] cyanation, 19 azidination 20 (Fig. 1a).…”