title: Combining organometallic reagents, the sulfur dioxide surrogate DABSO, and amines: a one-pot preparation of sulfonamides, amenable to array synthesis.
abstract: We describe a method for the synthesis of sulfonamides through the combination of an organometallic reagent, a sulfur dioxide equivalent, and an aqueous solution of an amine under oxidative conditions (bleach). This simple reaction protocol avoids the need to employ sulfonyl chloride substrates, thus removing the limitation imposed by the commercial availability of these reagents. The resultant method allows access to new chemical space, and is also tolerant of the polar functional groups needed to impart favorable physiochemical properties required for medicinal chemistry and agrochemistry. The developed chemistry is employed in the synthesis of a targeted 70 compound array, prepared using automated methods. The array achieved a 93% success rate for compounds prepared. Calculated molecular weights, lipophilicities, and polar surface areas are presented, demonstrating the utility of the method for delivering sulfonamides with drug-like properties.
authors.affiliation: Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA (UK) http://mcwillis.chem.ox.ac.uk/MCW/Home.html.
authors.forename: Alex S
authors.initials: AS
authors.lastname: Deeming
authors.forename: Claire J
authors.initials: CJ
authors.lastname: Russell
authors.forename: Michael C
authors.initials: MC
authors.lastname: Willis
mesh_terms: D000588:Amines / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry; D010084:Oxidation-Reduction; D010879:Piperazines / Q000737:chemistry*; D013441:Sulfinic Acids / Q000737:chemistry; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry; D013458:Sulfur Dioxide / Q000737:chemistry*
chemical_list: D000588:Amines; D009942:Organometallic Compounds; D010879:Piperazines; D013441:Sulfinic Acids; D013449:Sulfonamides; D013458:Sulfur Dioxide; C044255:sulfonyl chloride; C007306:triethylenediamine
keywords: amines; array synthesis; organometallics; physiochemical properties; sulfonamides