Cyclic peptides are valued synthetic targets in organic and medicinal chemistry. Herein, we report an efficient strategy for the synthesis of unnatural cyclic peptides via the Cu-catalyzed 1,3-dipolar cycloaddition of azomethylene ylides. Linear precursors of different lengths and bearing diverse amino acids (26 examples) are shown to be compatible with this method, affording good yields and complete -diastereoselectivities. Density functional theory (DFT) calculations support a stepwise mechanism in which Cu plays a key role in the preorganization of the reactants.

A chemoselective amino-based probe was designed for discovering natural products with covalent binding potential to lysine. Using this reactivity-based technique, a marine-derived strain was identified, which could produce medermycin as the major metabolite. A new compound, mederpyrrole A, derived from medermycin and anthranilic acid through nonenzymatic reaction was isolated. Medermycin can react with primary amines under mild conditions to generate chimeric products possessing a naphthoquinone-pyrrole skeleton. It can also covalently bind to proteins.

An efficient and highly enantioselective synthesis of tipranavir is realized based on an iridium-catalyzed asymmetric allylic substitution. High yield and diastereoselectivity (>20:1), as well as excellent enantioselectivity (99% ), were obtained for the key intermediate through direct asymmetric alkylation reaction of dihydropyranone with allylic -butyl carbonate. Anti-AIDS drug of tipranavir was finally accomplished in 8 steps and 6 pots starting from commercially available 1-phenyl-3-hexanone in 20.7% overall yield with 99% and >20:1 .

C-P bond formation has typically been achieved by a single-electron transfer process. Herein, a novel class of oxime ester bifunctionalization reagents were first applied to the photocatalytic β-aminophosphorylation of modular olefins. The bifunctional reagents generate two distinct radical species (imine and phosphoryl radicals) that exhibit excellent regioselectivity. Subsequently, these radicals are attached to the olefins through a single-step EnT catalytic process, establishing a novel synthetic pathway. This protocol is characterized by excellent regioselectivity, broad functional group tolerance, and mild reaction conditions, which would enrich the diversity and versatility to facilitate the diversity-oriented synthesis of β-aminophosphorylated complex molecule scaffolds.

Regioselective hydroaminative cyclizations of 1,5- and 1,6-diynes via double functionalization of an alkyne carbon were achieved using a phosphine-quinolinolato (PNO) rhodium catalyst. While the reaction of 1,6-diynes with secondary amines provided cyclic 2-aminodienes, phenylene-tethered 1,5-diynes were transformed into benzofulvene derivatives. The reaction is considered to proceed via in situ construction of an aminocarbene ligand, [2 + 2] addition with an internal alkyne moiety, and isomerization to an aminodiene structure. This hydroaminative cyclization proceeds just by heating the substrate with the rhodium catalyst without adding any additive and provides a convenient route to access cyclic 2-aminodiene and aminobenzofulvene derivatives.

-directed 2-fold bromoboration reactions of diynes with BBr have been developed, allowing the access to novel internally BN-doped polycyclic aromatic hydrocarbons from readily available precursors under mild conditions. Computational investigations identified three potential reaction mechanisms, each involving either BBr or [BBr], with low activation barriers ( < 16 kcal/mol) for all pathways. The resulting brominated products can be further functionalized through various cross-coupling protocols, enabling the synthesis of highly luminescent emitters with quantum yield exceeding 90.

Stereo- and enantioselective syntheses of 1,2-oxaborinan-3-enes and δ-boryl-substituted homoallylic alcohols are reported. We developed a practical approach to synthesize α-boryl-substituted allylboronate. This reagent was utilized to generate α,α-disubstituted allylboronates, and such reagents cannot be accessed via the Pd-catalyzed alkene isomerization approach. Chiral Brønsted-acid-catalyzed aldehyde addition with these reagents gave 1,2-oxaborinan-3-enes with excellent stereo- and enantioselectivities. Lewis-acid-catalyzed aldehyde addition also worked well, affording δ-boryl-substituted homoallylic alcohols with high stereoselectivities. The enantioselective variant of the reaction was achieved via a chiral Brønsted-acid-catalyzed aldehyde addition and Pd-catalyzed alkene isomerization approach.

Herqupenoid A (), a sesquiterpene-quinone hybrid with an unparalleled 5/5/6/5-fused ring skeleton based on a multicyclic caged 2,7-dioxatetracyclo[5.4.0.0.0]hendecane fragment, was isolated from fungus . Its structure was assigned by extensive spectroscopic analyses, DP4+ computational method, and single-crystal X-ray diffraction. Further pharmacology research has established that compound exhibited significant anti-inflammatory activity via inhibiting NF-κB-NLRP3 axis with an IC value of 2.63 μM, which was stronger than the positive control dexamethasone. A putative biosynthetic pathway involving the key hemiacetal and aldol condensation reactions for was also discussed.

An efficient FLP-mediated cycloisomerization is described, providing easy access to quinolinium and chromenylium derivatives by treatment of readily available propargylanilines and aryl propargyl ethers with Lewis acidic boranes, respectively. The reaction proceeds via a 6--dig cyclization/dehydrogenation sequence. The heteroatom functions serve as Lewis bases in combination with Lewis acidic boranes to effect synergistic activation of an alkynyl triple bond and a C-H bond.

Sulfur-containing compounds represent a significant category of organic compounds, and the introduction of sulfur groups into organic compounds can effectively enhance their biological activity and synthetic diversity. Although a variety of difunctionalization reactions of alkenes based on sulfur radicals have been documented, significant challenges remain in the carbonylative difunctionalization of unactivated alkenes by the addition of a sulfur radical. Herein, we present a trifluoromethylthiolative carbonylation reaction of unactivated alkenes, which goes through the addition of a trifluoromethylthiol radical to unactivated alkenes and then carbonylation of the newly generated carbon radical intermediate. A heterocyclic/aryl migration in the presence of carbon monoxide is crucial for the success of this methodology and finally resulted in the formation of sulfur-containing carbonylated products in good yields.

We developed a water-promoted cross-coupling of 3-hydroxyisobenzofuran-1(3)-ones and allylic boronates under biocompatible conditions. This approach facilitates the synthesis of diverse 3-allylic phthalides with high yields and exceptional selectivity in a metal-free manner. The versatility and practicality of this protocol underscore its significant potential for drug development and applications in medicinal chemistry.

We report herein a visible-light photoredox-catalyzed 1,4-hydrofluoromethylation of terminal-alkene-derived 1,3-enynes with sodium fluoromethylsulfinate, providing an effective protocol to access a diversity of di- and trisubstituted allenes under mild conditions. The synthetic utility of the present protocol was demonstrated by a large-scale reaction as well as the synthetic derivatization of the allene product.

A Pd-catalyzed asymmetric Heck cascade reaction involving the intramolecular carbopalladation of unsaturated hydrocarbons, followed by nucleophilic trapping of the resulting palladium species, is a powerful approach for constructing chiral -heterocycles. However, the use of prochiral nucleophiles in these reactions remains significantly underexplored. Herein, we report a novel Pd/Cu catalytic system for the asymmetric cascade Heck/Tsuji-Trost reaction of allenamides and aldimine esters. This robust method allows for the rapid synthesis of a wide range of enantiopure non-natural α-substituted tryptophans in high yields (up to 99% yield) with excellent enantioselectivities (up to 98% ee). Additionally, the synthetic utility of this protocol is demonstrated through scale-up experiments and diverse valuable transformations.

4-Amino-5-nitro-7-pyrazolo[3,4-][1,2,3]triazine-2-oxide () is synthesized via one step in this study. Subsequently, 4,7-diamino-5-nitro-pyrazolo[3,4-][1,2,3]triazine-2-oxide (), 4-oxo-5-nitro-7-pyrazolo[3,4-][1,2,3]triazine-2-oxide (), and several heat-resistant salts are synthesized through local structural modifications on . Comparison of thermal stability between and indicates that while the amino group has a negative impact on the thermal stability of , it enhances the detonation performance of and effectively reduces its mechanical sensitivity. Our findings provide a practical new approach for constructing energetic materials with excellent stability.

A photocatalytic hydroamidomethylation of azobenzenes with ,-dimethylamides has been developed. Using tetrabutylammonium decatungstate (TBADT) as a photocatalyst, an array of azobenzenes and ,-dimethylamides reacted smoothly under visible light irradiation, affording previously unreported -amidomethyl-,'-diarylhydrazines in generally high yields. Mechanistic studies indicate that the reaction is enabled by TBADT-mediated hydrogen atom transfer (HAT) photocatalysis. This work is fundamentally different from the previously reported reaction of ,-dimethylformamide with azobenzenes.

We have developed a photoinduced transition-metal-free decarbonylative strategy at ambient temperature through non-covalent interactions to achieve vinyl sulfones. Traditionally, decarbonylative functionalization is accomplished using transition metal catalysts at elevated temperatures. The π-π interaction facilitates the elimination of CO to generate vinyl radical, thereby promoting the creation of C-S bonds with the sulfonyl radical. These interactions and the overall process were illuminated by spectroscopic investigations and mechanistic studies.

Avoiding undesired intramolecular reactions during desired intermolecular reactions is an important challenge in synthetic organic chemistry. We successfully avoided undesired intramolecular diketopiperazine formation during desired N-alkylation in the synthesis of peptoids using a microflow reactor. Fifteen peptoids were synthesized in good to high yields, and a cyclic peptoid was synthesized on the gram scale using the developed microflow approach. The productivity and cost of our approach are significantly superior to those of the conventional solid-phase approach.

A regioselective radical α,γ-diphosphinylation of allylamines with secondary phosphine oxides by photoinduced cobaloxime catalysis is described. The reaction tolerates a wide range of allylamines and phosphine oxides, affording α-amino diphosphine dioxides in moderate to good yields with hydrogen evolution. The synthesis of new diphosphine monoxide and diphosphine ligands and the promising antitumor activities of products demonstrate the great potential applications of this approach in catalysis and drug discovery. The detailed mechanism studies indicate that this reaction likely proceeds through a dehydrogenative allylic phosphinylation and nucleophilic addition process.

This study demonstrates a method that utilizes arc plasma-induced microdroplet reactions to synthesize dual-activated products with C(sp)-N and C(sp)-O bonds starting from C-H bonds. This innovative process utilizes arc- and microdroplet-generated hydroxyl radicals and water dimer radical cations, opening new possibilities for the multisite derivatization of small molecules.

The step-economical synthesis of pyrrole derivatives has posed a challenge in the field of -heterocyclic chemistry. A novel photocascade catalytic radical S2'-type reaction/radical addition/annulation sequence of MBH acetates provides a straightforward route to pyrrole derivatives by forming new C-C, C-N, and C═C bonds in one pot, using -arylglycines as the α-arylaminomethyl radical precursors for double insertion.

Cyclometalated ruthenium(II)-complex-catalyzed selective oxidative scission of olefins to carbonyls is described. A strong C-donor ligand, paired with a rigid backbone and redox activity of ruthenium, provided high catalytic activity and a long lifetime for olefin oxidation. The catalyst tolerates numerous functional groups and applies to challenging biomass-, natural-product-, sugar-, amino-acid-, and fatty-acid-derived substrates.