[3 + 1]- and [3 + 2]-Cycloadditions of Azaoxyallyl Cations and Sulfur Ylides

A new formal [3 + 1]-cycloaddition reaction of azaoxyallyl cation intermediates, generated in situ from α-halo hydroxamates bearing α-alkyl groups, and sulfur ylides is reported, furnishing useful β-lactams (dr >19:1) in fair to modest yields. In contrast, an unexpected formal [3 + 2]-cycloaddition reaction occurs to give γ-lactam derivatives for α-halo hydroxamates with α-aryl groups and sulfur ylides in the presence of bases

Trisubstituted Sulfonamides: A New Chemotype for Development of Potent and Selective CB₂ Receptor Inverse Agonists

An extensive exploration of the structure–activity relationship of a trisubstituted sulfonamide series led to the identification of <b>39</b>, which is a potent and selective CB₂ receptor inverse agonist [<i>K</i>_i(CB₂) = 5.4 nM, and <i>K</i>_i(CB₁) = 500 nM]. The functional properties measured by cAMP assays indicated that the selected compounds were CB₂ inverse agonists with high potency values (for <b>34</b>, EC₅₀ = 8.2 nM, and for <b>39</b>, EC₅₀ = 2.5 nM). Furthermore, an osteoclastogenesis bioassay indicated that trisubstituted sulfonamide compounds showed great inhibition of osteoclast formation

[3 + 1]- and [3 + 2]-Cycloadditions of Azaoxyallyl Cations and Sulfur Ylides

A new formal [3 + 1]-cycloaddition reaction of azaoxyallyl cation intermediates, generated in situ from α-halo hydroxamates bearing α-alkyl groups, and sulfur ylides is reported, furnishing useful β-lactams (dr >19:1) in fair to modest yields. In contrast, an unexpected formal [3 + 2]-cycloaddition reaction occurs to give γ-lactam derivatives for α-halo hydroxamates with α-aryl groups and sulfur ylides in the presence of bases

Turn-On Fluoresence Sensor for Hg²⁺ in Food Based on FRET between Aptamers-Functionalized Upconversion Nanoparticles and Gold Nanoparticles

In this study, a turn-on nanosensor for detecting Hg²⁺ was developed based on the fluorescence resonance energy transfer (FRET) between long-strand aptamers-functionalized upconversion nanoparticles (UCNPs) and short-strand aptamers-functionalized gold nanoparticles (GNPs). In the absence of Hg²⁺, FRET between UCNPs and GNPs occurred because of the specific matching between two aptamers, resulting in the fluorescence quenching of UCNPs. In the presence of Hg²⁺, long-stranded aptamers fold back into a hairpin structure due to the stable binding interactions between Hg²⁺ and thymine, leading to the release of GNPs from UCNPs, resulting in the quenched fluorescence restoration. Under the optimized conditions, the nanosensor achieved a linear detection range of 0.2–20 μM and a low detection limit (LOD) of 60 nM. Meanwhile, it showed good selectivity and has been applied to detecting Hg²⁺ in tap water and milk samples with good precision

α‑Regioselective Asymmetric [3 + 2] Annulations of Morita–Baylis–Hillman Carbonates with Cyclic 1‑Azadienes and Mechanism Elucidation

An α-regio-, diastereo-, and enantioselective [3 + 2] annulation reaction of Morita–Baylis–Hillman carbonates of isatins and activated alkenes with a bulky electron-withdrawing 1,2-benzoisothiazole 1,1-dioxide or 1,2,3-benzoxathiazine 2,2-dioxide motif is reported, furnishing an array of spirooxindoles (>19:1 dr, up to >99% ee) catalyzed by cinchona-derived tertiary amines. Density functional theory calculation studies have been conducted to elucidate the originality of the α-regioselective annulations

Regio- and Diastereodivergent [4 + 2] Cycloadditions with Cyclic 2,4‑Dienones

By employing activated alkenes with bulky α-functional groups, such as α-cyano-α,β-unsaturated ketones and Meldrum’s acid–based alkenes, a previously unreported cross-trienamine pathway of cyclic 2,4-dienones is adopted to deliver γ′,δ-regioselective [4 + 2] cycloadducts catalyzed by cinchona-derived amines. In addition, a diastereodivergent [4 + 2] cycloaddition reaction is realized with <i>Z</i>-configured 4-alkylidene­isoxazol-5­(4<i>H</i>)-ones under similar catalytic conditions, even through a three- or four-component cascade process with simple starting materials

α‑Regioselective Asymmetric [3 + 2] Annulations of Morita–Baylis–Hillman Carbonates with Cyclic 1‑Azadienes and Mechanism Elucidation

An α-regio-, diastereo-, and enantioselective [3 + 2] annulation reaction of Morita–Baylis–Hillman carbonates of isatins and activated alkenes with a bulky electron-withdrawing 1,2-benzoisothiazole 1,1-dioxide or 1,2,3-benzoxathiazine 2,2-dioxide motif is reported, furnishing an array of spirooxindoles (>19:1 dr, up to >99% ee) catalyzed by cinchona-derived tertiary amines. Density functional theory calculation studies have been conducted to elucidate the originality of the α-regioselective annulations

Use of (<i>E</i>,<i>E</i>)‑Dienoic Acids as Switchable (<i>E</i>,<i>E</i>)- and (<i>Z</i>,<i>E</i>)‑Dienyl Anion Surrogates via Ligand-Controlled Palladium Catalysis

Carboxylic acids are not readily applied as carbon-based nucleophiles due to their intrinsic acidic group. Here, we demonstrate that free (E,E)-2,4-dienoic acids form electron-neutral and highest occupied molecular orbital-raised η2-complexes with Pd(0) and undergo Friedel–Crafts-type additions to imines with exclusive α-regioselectivity, giving formal dienylated products after decarboxylation. Unusual and switchable (E,E)- and (Z,E)-selectivity, along with excellent enantioselectivity, is achieved via ligand-controlled outer-sphere or inner-sphere reaction modes, respectively, which are well supported by comprehensive density functional theory calculation studies. An unprecedented formal reductive Mannich reaction between (E,E)-dienoic acids and imines is also developed to furnish enantioenriched β-amino acid derivatives

Chiral Aldehyde Catalysis for the Catalytic Asymmetric Activation of Glycine Esters

Chiral aldehyde catalysis is uniquely suitable for the direct asymmetric α-functionalization of N-unprotected amino acids, because aldehydes can reversibly form imines. However, there have been few successful reports of these transformations. In fact, only chiral aldehyde catalyzed aldol reactions of amino acids and alkylation of 2-amino malonates have been reported with good chiral induction. Here, we report a novel type of chiral aldehyde catalyst based on face control of the enolate intermediates. The resulting chiral aldehyde is the first efficient nonpyridoxal-dependent catalyst that can promote the direct asymmetric α-functionalization of N-unprotected glycine esters. Possible transition states and the proton transfer process were investigated by density functional theory calculations

Chiral Aldehyde Catalysis for the Catalytic Asymmetric Activation of Glycine Esters

Chiral aldehyde catalysis is uniquely suitable for the direct asymmetric α-functionalization of N-unprotected amino acids, because aldehydes can reversibly form imines. However, there have been few successful reports of these transformations. In fact, only chiral aldehyde catalyzed aldol reactions of amino acids and alkylation of 2-amino malonates have been reported with good chiral induction. Here, we report a novel type of chiral aldehyde catalyst based on face control of the enolate intermediates. The resulting chiral aldehyde is the first efficient nonpyridoxal-dependent catalyst that can promote the direct asymmetric α-functionalization of N-unprotected glycine esters. Possible transition states and the proton transfer process were investigated by density functional theory calculations