We describe the implementation of an iron catalyzed cyano-fluoroalkylation of unactivated alkenes that leverages inexpensive trifluoroacetic acid (CF3CO2H) and related carboxylic acids (CFnRCO2H) as radical fluoroalkyl sources, together with tosyl cyanide (TsCN) as a low-toxicity cyanation reagent. Notably, the mild and redox-neutral conditions of the method are compatible with a broad range of substrates, including alkenes containing biologically relevant motifs (40 examples, up to 83% yield). The resulting β-fluoroalkylated nitriles can be diversely derivatized to afford other valuable fluorinated sp3-rich architectures. Mechanistic studies have revealed the key role of a protonated bipyridine-based ligand in enhancing reaction efficiency.

Rugonidines A-F are a family of structurally unique diastereomeric alkaloids characterized by an unprecedented [4.5]-fused N-alkoxyguanidinyl spiroketal ring system. This work reports the first synthesis of this motif via an acid-catalyzed, one-pot tandem deprotection/cyclization cascade of a protected N-hydroxyguanidine intermediate, efficiently forging the target spirocyclic framework in 21% yield over nine steps. X-ray crystallographic analysis unambiguously confirmed structural connectivity, providing the first solid-state characterization of this unusual architecture.

Herein, we report a practical metal- and additive-free method for transfer hydrogenation of nitrones, employing a readily available PhSiH3 as the hydrogen donor. The findings demonstrated the effective conversion of a wide range of ketone- and aldehyde-derived nitrones into their corresponding hydroxylamine derivatives in good to excellent yields under mild conditions. The reaction is readily scalable and demonstrates broad functional group tolerance, accommodating bromo, chloro, fluoro, trifluoromethyl, thioether, thiophene, and furan substituents. Hence, the proposed operationally simple protocol provides a practical and sustainable strategy, facilitating the synthesis of structurally diverse hydroxylamine derivatives.

An efficient synthesis of epitopes of PGL-I glycolipids of Mycobacterium leprae was achieved using the 4-methoxyphenyl (MP) group as dual-mode Janus aglycone. Cleavage of the MP aglycone in a disaccharide gave a hemiacetal precursor of the glycosyl donor that was used for the assembly of the trisaccharide PGL-I epitope through α-selective [2+1] rhamnosylation (96:4 α:β). Selective demethylation of the MP aglycone in di- and trisaccharides followed by alkylation of the resulting phenolic hydroxy group gave diverse spacer aglycones suitable for the synthesis of neoglycoconjugates.

We demonstrate the chemoselective 2-deoxyglycosylation of formidable C-4 equatorial glycals enabled by a conformationally constrained protecting-group strategy. A proof-of-principle for the Bi(OTf)3-mediated 2-deoxyglycosylation of trans-fused 3,4-O-TIPDS-protected l-rhamnal, d-glucal, and d-xylal is illustrated using carbohydrates, amino-acids, and bioactive-natural products, providing structurally diverse 2-deoxy and 2,6-dideoxyglycoconjugates. Mechanistic insights into the distinctive structures of the glycosyl species revealed that conformational locking restricts the accessible 5H4 glycal and 4H3 oxocarbenium ion conformations, thereby favoring 1,2-addition and circumventing the Ferrier pathway.

The hexafluoroisopropanol (HFIP)-assisted thermal denitrogenative fragmentation of areneazo-2-(2-nitro)propanes enabled heteroarylation of functionalized alkenes through cooperative radical and redox processes. Bench-stable areneazo-2-(2-nitro)propanes served as versatile aryl radical precursors for carboheterocyclization with alkenyl esters, affording diverse arylated lactones and heterocycles with broad functional group tolerance. Mechanistically, the radical fragmentation-nitro-nitrite isomerization of areneazo-2-(2-nitro)propanes generated nitric oxide that underwent a redox process with tertiary radical intermediates to promote heterocyclization. The oxidant-free conditions generated dinitrogen and acetone as benign byproducts.

We report a phosphine-catalyzed [3 + 2] annulation of indole N-alkynamides with ynones, providing efficient access to arylidene spiro-cyclopentanone pyrroloquinolinediones. The reaction proceeds through the in situ generation of a reactive enedione intermediate and exhibits broad substrate scope, high regioselectivity, and gram-scale applicability. Mechanistic studies support the involvement of transient enedione and phosphine-derived zwitterionic intermediates. This strategy unveils a previously unexplored reactivity of indole N-alkynamides and enables rapid construction of structurally unique spirocyclic frameworks.

An efficient and general method for the synthesis of highly functionalized bicyclo[4.2.0]trienes via a palladium-catalyzed self-dimerization annulation of β-CF3-1,3-enynamides and cross-dimerization annulation of β-CF3-1,3-enynamides with 1,3-enynes was developed. β-CF3-1,3-enynamides bearing a Ts group were identified as optimal reagents for cross-dimerization of two different enynes. In all cases, the reactions proceeded in a regiospecific manner, affording highly functionalized bicyclo[4.2.0]trienes which are challenging to prepare via conventional approaches. Further synthetic transformations of the bicyclo[4.2.0]trienes were explored, highlighting their distinctive reactivity profile and outlining their application in diverse syntheses.

We report arene-, stereo-, and regioselective functionalizations of biaryl compounds (A-A') with α-cyanodiazoacetates via Rh(II)-catalyzed enantioselective Buchner dearomatization. Density functional theory calculations suggest that selectivity for ring A' of A-A' biaryl and regioselectivity on arene A' are both determined by steric effects, resulting in high constitutional isomer selectivity among the ≤12 possible. Electron-withdrawing and -donating groups on ring A retain high site selectivity, despite the latter activating ring A toward electrophilic Rh(II)-carbenoid.

A new class of chiral bis-urea-embedded pillararenes, each containing two chiral bis-urea units, was synthesized through a modular two-step strategy. Efficient chirality transfer affords well-defined all-pS or all-pR planar chirality, with the corresponding chiroptical responses remaining essentially unchanged over the investigated temperature range. Remarkably, macrocyclization of racemic precursors undergoes spontaneous chiral self-sorting to preferentially afford homochiral macrocycles. This strategy provides a new approach to the generation and stabilization of planar chirality in pillararenes.

The synthesis of dialkylamino bicyclo[1.1.1]pentanes (BCPs) has been hindered by the weakly nucleophilic and hydrogen atom transfer (HAT)-prone nature of dialkylaminyl radicals, which precludes their use in strain-release functionalization of [1.1.1]propellane. Herein, we report a photoredox-catalyzed three-component strain-release dialkylamino-heteroarylation of [1.1.1]propellane using secondary amines with NCS via dialkylaminyl radicals. This mild protocol provides modular access to structurally diverse alkylamines in a single operation, accommodating a wide range of amines and N-heterocycles to afford products in moderate to excellent yields. Gram-scale synthesis, late-stage functionalization of complex natural products and drugs, and mechanistic studies collectively support the proposed radical pathway and demonstrate the synthetic utility of this protocol.

Dehydroamino acids are found in natural products, disease-associated proteins, and are used for the diversification of proteins and peptides. The synthesis of peptide sequences containing dehydroamino acids remains nontrivial and only a few chemical methods allow for their incorporation. We report the conversion of amino acid residues bearing β-thiols into dehydroamino acids through the treatment of unprotected peptides and proteins with cyanamide under mild, fully aqueous conditions that are compatible with commonly used buffer salts.

Herein, we report a nickel-catalyzed asymmetric hydrophosphination of phosphine-borane-derived alkynes. This method delivers a series of structurally novel P-stereogenic bisphosphine derivatives. A broad range of alkynes and secondary phosphines was tolerated. The resulting bisphosphine products can be readily converted to P-chiral bisphosphine ligands by in situ deprotection. Using this strategy, we synthesized a series of chiral transition metal complexes that hold great promise for homogeneous catalysis.

Chiral aza[3.1.0]bicyclic scaffolds and the acrylonitriles represent privileged structural motifs in numerous bioactive molecules and pharmaceuticals. Herein, we report a highly efficient palladium-catalyzed asymmetric bicyclization/cyanation reaction of propargylic ester-tethered 1,6-enynes, using Zn(CN)2 as the cyanide source. This transformation proceeds through a cascade sequence involving oxidative addition, isomerization, bicyclization, and cyanation, enabling the rapid construction of chiral aza[3.1.0]bicycles bearing an alkenyl nitrile moiety in good yields and with outstanding enantioselectivities.