Light-enabled scalable synthesis of bicyclo[1.1.1]pentane halides and their functionalizations.

In 2012, bicyclo[1.1.1]pentanes were demonstrated to be bioisosteres of the benzene ring.

SAr or Sulfonylation? Chemoselective Amination of Halo(het)arene Sulfonyl Halides for Synthetic Applications and Ultralarge Compound Library Design.

The chemoselectivity of halo(het)arene sulfonyl halide aminations is studied thoroughly under parallel synthesis conditions, and the scope and limitations of the method are established. It is shown that SAr-reactive sulfonyl halides typically undergo sulfonamide synthesis during the first step; the second amination is also possible provided that the SAr-active center is sufficiently reactive. On the contrary, sulfonyl fluorides bearing an arylating moiety undergo selective transformation at the latter reactive center under proper control.

Direct mapping of ligandable tyrosines and lysines in cells with chiral sulfonyl fluoride probes.

Advances in chemoproteomic technology have revealed covalent interactions between small molecules and protein nucleophiles, primarily cysteine, on a proteome-wide scale. Most chemoproteomic screening approaches are indirect, relying on competition between electrophilic fragments and a minimalist electrophilic probe with inherently limited proteome coverage. Here we develop a chemoproteomic platform for direct electrophile-site identification based on enantiomeric pairs of clickable arylsulfonyl fluoride probes.

Synthesis of α--Stereochemically Pure Secondary Sulfonamides.

A convenient "green" stereoretentive approach to -enriched secondary sulfonamides bearing an asymmetric center at the α position to the sulfur atom is described. The method relies on the electrophilic amination of the corresponding stereochemically pure sulfinates with -alkylhydroxylamine sulfonic acids (in turn easily prepared from -alkylhydroxylamine and HSOCl). It is shown that the efficiency of the approach is governed mainly by steric factors; its tolerance to several functional groups (e.

Synthesis of spirocyclic β- and γ-sultams by one-pot reductive cyclization of cyanoalkylsulfonyl fluorides.

One-pot intramolecular cyclization of novel sp-enriched cyanoalkylsulfonyl fluorides into spirocyclic β- or γ-sultams is disclosed. The method relies on nitrile group reduction followed by sulfonylation of amino group thus formed upon mild conditions (NaBH, NiCl·6HO in MeOH). Cyclization proceeds smoothly with considerable efficiency (48-84%, 10 examples) on up to 30 g scale.

Large-Scale Synthesis and Modifications of Bicyclo[1.1.1]pentane-1,3-dicarboxylic Acid (BCP).

photochemical addition of propellane to diacetyl allowed construction of the bicyclo[1.1.1]pentane (BCP) core in a 1 kg scale within 1 day.

Twisting and Turning the Sulfonamide Bond: A Synthetic, Quantum Chemical, and Crystallographic Study.

Structural restriction of the sulfonamide bond was used to design sultams with abnormal geometric parameters. Based on analysis of tertiary aliphatic sulfonamides published in the Cambridge crystallographic database, Paquette's sultams (i.e.

Sulfonimidamides and Imidosulfuric Diamides: Compounds from an Underexplored Part of Biologically Relevant Chemical Space.

Two novel solid reagents-1-sulfonimidoyl- and 1-sulfamimidoyl-3-methylimidazolium derivatives-for the synthesis of sulfonimidamides and imidosulfuric diamides, respectively, were developed. It is shown that these reagents are very effective in substitution reactions with various N- and O-nucleophiles; therefore, they significantly extend the accessibility to the chemical space covered by organosulfur(VI) compounds with S=N bonds. In addition, previously unknown imidosulfuric diamides with free imino nitrogen groups were prepared, and their physical and chemical properties were characterized (including molecular geometry, pK , Log P, microsomal stability, and reactivity towards typical electrophiles).