Dataset Information

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.

SUBMITTER: Deeming AS

PROVIDER: S-EPMC4312890 | biostudies-other | 2015 Jan

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Combining organometallic reagents, the sulfur dioxide surrogate DABSO, and amines: a one-pot preparation of sulfonamides, amenable to array synthesis.

Deeming Alex S AS Russell Claire J CJ Willis Michael C MC

Angewandte Chemie (International ed. in English) 20141127 4

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 ...[more]

PMID: 25431118

Similar Datasets

Project description:Reactions of three magnesium(i) dimers, [{(ArNacnac)Mg-}2] (ArNacnac = [(ArNCMe)2CH]-; Ar = xylyl (Xyl), mesityl (Mes) or 2,6-diethylphenyl (Dep)), with either 1,1-diphenylethylene (DPE), ?-methylstyrene (MS), trans-stilbene (TS) or diphenylacetylene (DPA) led to the 1,2-addition of the Mg-Mg bond across the substrate, giving rise to the 1,2-dimagnesioethanes, [{(XylNacnac)Mg}2(?-DPE)], [{(DepNacnac)Mg}2(?-MS)], [{(ArNacnac)Mg}2(?-TS)] (Ar = Mes or Dep); and a 1,2-dimagnesioethene, [{(MesNacnac)Mg}2(?-DPA)]. The reactions involving the 1,1-substituted alkenes are shown to be readily redox reversible, in that the reaction products are in equilibrium with a significant proportion of the starting materials at room temperature. Variable temperature NMR spectroscopy and a van't Hoff analysis point to low kinetic barriers to these weakly exergonic reactions. [{(MesNacnac)Mg}2(?-DPE)] and [{(MesNacnac)Mg}2(?-DPA)] behave as 1,2-di-Grignard reagents in their reactions with very bulky amido-zinc bromides, yielding the first examples of a 1,2-dizincioethane, [(L*Zn)2(?-DPE)] (L* = -N(Ar*)(SiPri 3); Ar* = C6H2Me{C(H)Ph2}2-4,2,6), and a 1,2-dizincioethene, [(TBoLZn)2(?-DPA)] (TBoL = -N(SiMe3){B(DipNCH)2}, Dip = 2,6-diisopropylphenyl), respectively. Divergent reactivity is shown for [{(MesNacnac)Mg}2(?-DPE)], which behaves as a two-electron reducing agent when treated with amido-cadmium and amido-magnesium halide precursors, yielding the cadmium(i) and magnesium(i) dimers, [PhBoLCdCdPhBoL] (PhBoL = -N(SiPh3){B(DipNCH)2}) and [L†MgMgL†] (L† = -N(Ar†)(SiMe3); Ar† = C6H2Pri{C(H)Ph2}2-4,2,6), respectively. A further class of reactivity for [{(MesNacnac)Mg}2(?-DPE)] derives from its reaction with the bulky amido-germanium chloride, L*GeCl, which gives a magnesio-germane, presumably via intramolecular C-H activation of a highly reactive magnesiogermylene intermediate, [:Ge(L*){Mg(MesNacnac)}]. [{(MesNacnac)Mg}2(?-DPE)] can be considered as acting as a two-electron reducing, magnesium transfer reagent in this reaction.

Dataset Information

Combining organometallic reagents, the sulfur dioxide surrogate DABSO, and amines: a one-pot preparation of sulfonamides, amenable to array synthesis.

Publications

Combining organometallic reagents, the sulfur dioxide surrogate DABSO, and amines: a one-pot preparation of sulfonamides, amenable to array synthesis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure