We report a catalyst-free, regioselective [3 + 2] cycloaddition reaction between benzofuran-derived azadienes (BDAs) and N,N'-cyclic azomethine imines, where regioselectivity is controlled by modulating solvent polarity. Spiro[benzofuran-2,2'-pyrazolo[1,2-a]pyrazole] is obtained in high yields (up to 93%) using acetonitrile as the solvent, while the novel spiro[benzofuran-2,1'-pyrazolo[1,2-a]pyrazole] forms in moderate to good yields (42%-73%) with carbon tetrachloride. This solvent-controlled protocol exhibits excellent diastereoselectivity (dr >20:1) for both products, along with a broad substrate scope. Furthermore, scale-up experiments and derivatization studies have been successfully performed. This protocol provides an efficient strategy for regioselective control in the diversified synthesis of bicyclic pyrazolidines, offering a new approach for constructing bicyclic pyrazolidines with different configurations.

Catalyst- and solvent-free reaction of pyridine-d5 with secondary phosphine oxides and sulfides and phosphinic acid esters in the presence of benzoylphenylacetylene (50-55 or 70-75 °C, 7-35 h) gives 4-phosphorylated pyridines-d4 and -d3 (the latter having hydrogen at position 2) in 43-73% total yield along with differently deuterated chalcones, the reduced benzoylphenylacetylene. The scrutinized analysis of deuterium distribution in the above substitution products with emphasis on protium insertion in the pyridine ring reveals that the substitution studied involves the isomerization of the primary 1,3(4)-dipole intermediate to carbene localized at the position 2. Quantum chemical calculations (B3LYP/6-311++G**) indicate that diphenylphosphine oxide or trace water likely mediates the carbene generation stage.

Monoamine oxidase-A and -B are important flavoenzymes involved in the oxidative metabolism of various biogenic amines. Mechanisms including polar/nucleophilic, hydride transfer, and single electron transfer (SET) have been proposed for the initial steps of the catalytic mechanism. The most compelling evidence for the latter comes from the observed inhibitory behavior of N-cyclopropyl compounds. Enzyme inactivation presumably occurs when the primary radical portion of the distonic radical cation, resulting from cyclopropyl ring opening, couples to the enzyme. Previously, we hypothesized that the unique substrate behavior of 1,4-disubstituted-1,2,3,6-tetrahydropyridinyl systems was attributable to certain structural features which activate the SET pathway. In the present work, the oxidation of several N-cyclopropyl derivatives of MPTP in a biomimetic system (3MLF/hν) is reported. Calculations suggest that the barrier to ring opening may not be as low as assumed, and experiments show the process is reversible. The results also suggest that the ring-opened (distonic) radical cation may disrupt the active site through radical coupling, hydrogen atom abstraction, or through reaction with O2 that can lead to reactive oxygen species. Hydrolysis of an intermediate iminium moiety leads to the production of low molecular weight aldehydes, which may also provide a pathway for enzyme inactivation.

Herein, we report an efficient palladium-catalyzed (2 + 2 + 1) cyclization strategy for the synthesis of polysubstituted pyrroles from enone oxime ethers, alkynes, and diaziridinone. This transformation is proposed to proceed through a cascade process involving C-C bond cleavage, migratory insertion of alkyne into the C-Pd bond, C-H activation, and subsequent amination with diaziridinone. Notably, this protocol enables the direct incorporation of bioactive fragments into the pyrrole skeleton, highlighting its synthetic utility in medicinal chemistry applications.

A visible-light-promoted and simple iron salt-catalyzed cascade amidation/cyclization of N-aryl acrylamides with dioxazolones was developed. The reaction proceeds under photosensitizer-free conditions and features satisfactory to good yields, broad functional group tolerance, and an easy operation procedure. Mechanistic studies revealed that the reaction proceeded via an iron-nitrene intermediate. This method may contribute to shift the paradigm of iron-catalyzed C-N bond construction and nitrene transfer chemistry.

We report a one-pot reaction of thioamides with α-trifluoromethylstyrenes to synthesize 1,3-thiazines with a fluorine atom directly incorporated into the core structure. The reaction proceeds via the SN2'/SNV pathway, preventing double defluorinative alkylation and enabling efficient cyclization under ultrasonic sonication. This method offers mild conditions, short reaction times, a broad substrate scope, high yields (up to 95%), and gram-scale applicability. DFT studies reveal kinetic control, with nitrogen attack favored over sulfur attack due to lower activation barriers.

A Mn(III)-promoted cascade arylation/cyclization of ortho-isocyano propargylanilines with aryl boronic acids has been developed. The protocol provides a novel and highly efficient access to construct two central rings (diazepine and cyclopenta-1,3-diene) of a tetracyclic product via the formation of three C-C bonds in one pot.

This study presents a novel, metal-free method for synthesizing conjugated dienyl esters through the base-catalyzed remote migratory nucleophilic substitution reaction of halopenta-1,4-diene derivatives. Experimental and density functional theory (DFT) calculations confirm that bromine not only acts as a leaving group but also modulates electronic distribution within the molecule. This facilitates a remote migratory process to form 5-bromopenta-1,3-diene from 1-bromopenta-1,4-diene, followed by nucleophilic addition with a carboxylate anion with a lower energy barrier of 25.9 kcal/mol, yielding a thermodynamically stable product.

A new method for the meta-arylation of pyridine N-oxides that employs o-diiodobenzene derivatives as convenient aryne precursors is reported. In contrast to the Kobayashi precursors, o-diiodobenzenes are either commercially available or readily prepared from simple starting materials and generate arynes under mild conditions via NaH-mediated activation. Our approach not only significantly expands the substrate scope of pyridine N-oxides but also offers an operationally simpler and complementary route to 3-arylpyridines.

We achieved the total syntheses of (±)-alanenses A, B, and lacinilene E using a unified strategy based on α-N-phthalimido-oxy isobutyrate (NPIB)-mediated deoxygenative C-C bond formation. Key improvements to McCormick's route to (±)-lacinilene C7-methyl ether enabled scalable access to common intermediates, while a streamlined de novo approach further enhanced the efficiency of the synthetic route. Importantly, a late-stage sequence of reductions, 9-I-9-BBN-mediated bis-demethylation, and DDQ oxidation overcame the previously encountered demethylation challenges to furnish the first synthetic sample of lacinilene E. This work demonstrates a convergent approach to cadinane sesquiterpenoids and showcases the versatility of NPIB-based chemistry.