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A silyl radical-mediated carbocyclization of acrylamide-/vinyl sulfonamide-attached alkylidenecyclopropanes via photoredox catalysis with a catalytic amount of silane reagent is reported in this pa...

Diversity-oriented synthesis embodied in a strategy of pairing vinyl sulfonamide moiety with other functional groups resulted in an array of skeletally diverse 5–8-membered sultams (cyclic sulfonamides) in the fewest possible steps. In particular, this strategy allows utilization of a number of cyclization protocols including intramolecular Michael, Diels–Alder, Heck, Pauson–Khand, Baylis–Hillman reactions, ring-closing metathesis (RCM) and others.

Synthetic DNA analogues are of great interest for their application in information storage, therapeutics, and nanostructured materials, yet are often limited in scalability. Vinyl sulfonamide click nucleic acids (VS-CNAs) have been developed to overcome this limitation using the highly efficient thiol-Michael 'click' reaction. Utilizing all four nucleobases, sequence-defined click nucleic acids (CNAs) were synthesized using a simple and scalabale solution-phase approach. Employing a polyethylene glycol (PEG) support, synthesis of the CNA sequence, GATTACA, was achieved in high yields. CNA crosslinked hydrogels were assembled using multiarm PEG-CNAs resulting in materials that dynamically respond to temperature, strain, and competitive sequences.

A series of seven- and eight-membered ring -N,O-, -N,N-, and -N,S-sultams were effectively synthesized via tandem reactions involving oxa-, aza-, and thia-Michael addition to vinyl sulfonamides. These reactions are summarized here since they enrich current synthetic methodologies for sultams and provide a good example of sultam diversity-oriented synthesis. All reactions proceeded under relatively mild and environmentally friendly conditions, and all these reactions are quite suitable for the rapid preparation of sultam compound libraries, which are valuable for biological activity explorations.

A one-pot, sequential protocol is reported that involves complementary ambiphile pairing (CAP) of a vinyl sulfonamide with a variety of unprotected amino acids via aza-Michael addition and subsequent intramolecular amidation. The method generates diverse, sp(3)-rich mono- and bicyclic acyl sultams in a highly scalable manner. Modular pairing of stereochemically rich building blocks allows quick access to all possible isomers. Extension to include one-pot, sequential 3-, 4-, and 5-multicomponent protocols is also discussed.

Five- and seven-membered sultam derivatives were conveniently synthesized via intra- or intermolecular Michael additions and an improved vinyl sulfonamide Baylis–Hillman reaction. Two different cyclization pathways were explored for the oxa-Michael reaction. A good solvent was discovered for an otherwise sluggish ketone-type Baylis–Hillman reaction in which vinyl sulfonamide ketones were used as the precursors. Furthermore, a strong base caused vinyl sulfonamide ketones to undergo 5-endo-trig intramolecular cyclizations, which are disfavored according to Baldwin's rule. Finally Baylis–Hillman reaction products were used as scaffolds for diversity-oriented sultam syntheses.

A gold-catalyzed olefin cyclopropanation reaction of propargyl esters with vinyl ester or vinyl sulfonamide derivatives was investigated for the synthesis of highly substituted cyclopropane derivatives in good diastereoselectivity. By varying the vinyl species, trans-cyclopentenyl esters were selectively formed by a formal [3+2] cycloaddition.

The construction of a 225-member (3 × 5 × 15) library of thiadiazepan-1,1-dioxide-4-ones was performed on a Chemspeed Accelerator (SLT-100) automated parallel synthesis platform, culminating in the successful preparation of 184/225 sultams. Three sultam core scaffolds were prepared based upon the utilization of an aza-Michael reaction on a multifunctional vinyl sulfonamide linchpin. The library exploits peripheral diversity in the form of a sequential, two-step [3 + 2] Huisgen cycloaddition/Pd-catalyzed Suzuki-Miyaura coupling sequence.

The formulation that the title compound, C18H18N2O4S2, adopts is a zwitterionic core with the charge separated to the sulfilimine S and N atoms and is supported by the two different S—N bond distances about the sulfinimine N atom [1.594 (2) and 1.631 (2) A° , respectively] that are typical for such bonds. The notably unusual bond is S—N(oxazolidinone) [1.692 (2) A°] that is longer than a typical S—N bond [1.603 (18) A° , Mogul analysis; Macrae et al. (2008). J. Appl. Cryst. 41, 466–470]. The bond-angle sum about sulfilimine sulfur (308.35 ) reflects the trigonal–pyramidal geometry of this atom. Two of the angles are less than 100. Despite the pyramidalization of this sulfur, there are no significant intermolecular interactions, beyond usual van der Waals contacts, in the crystal packing.

A one-pot, sequential protocol is reported that involves complementary ambiphile pairing (CAP) of a vinyl sulfonamide with a variety of unprotected amino acids via aza-Michael addition and subsequent intramolecular amidation. The method generates diverse, sp3-rich mono- and bicyclic acyl sultams in a highly scalable manner. Modular pairing of stereochemically rich building blocks allows quick access to all possible isomers. Extension to include one-pot, sequential 3-, 4-, and 5-multicomponent protocols is also discussed.

A new family of potent N-alkoxyvinylsulfonamide inhibitors of cruzain have been developed. Inhibitor 13 has a second order inactivation rate constant of 6,480,000s(-1)M(-1) versus cruzain, and is also highly effective against Trypanosoma cruzi trypomastigotes in a tissue culture assay.

A diversity-oriented synthesis (DOS) strategy termed “Click, Click, Cyclize” is reported. This approach relies on functional group (FG) pairing between a vinyl sulfonamide and an array of functional groups to synthesize skeletally diverse sultams. Several FG pairing pathways on central tertiary vinyl sulfonamide linchpins have been developed including intramolecular Heck, aza-Michael, ring-closing enyne metathesis, Pauson−Khand, and chemoselective oxidation/Baylis−Hillman reactions.

A diversity-oriented synthesis (DOS) strategy termed “Click, Click, Cyclize” is reported. This approach relies on functional group (FG) pairing between a vinyl sulfonamide and an array of functional groups to synthesize skeletally diverse sultams. Several FG pairing pathways on central tertiary vinyl sulfonamide linchpins have been developed including intramolecular Heck, aza-Michael, ring-closing enyne metathesis, Pauson−Khand, and chemoselective oxidation/Baylis−Hillman reactions.

The Michael reaction of phenyl vinyl sulfonate (3) or vinyl sulfonamide 12 with phenylacetic esters was the key step in a general synthesis of 4-phenyl-substituted 1,2-thiazane 1,1-dioxides (sultams) and 5-phenyl-1,2-oxathiane 1,1-dioxides (sultones). This methodology was applied to the synthesis of some cyclic sulfonamide and sulfonate derivatives (I and II) of the potent TXA 2 receptor antagonists BM.13177 and BM.03505

A variety of five-membered ring oxazoles have been synthesised with complete regiocontrol and without the requirement for ring oxidation via a reaction sequence based on a vinyl sulfonamide template.

A variety of five-membered ring oxazoles have been synthesised with complete regiocontrol and without the requirement for ring oxidation via a reaction sequence based on a vinyl sulfonamide template.