Organic Letters最新文献

Propargyl thiocyanates, which contain the alkynyl groupand SCNgroup, are significant building blocks in organic synthesis. However,there is a lack of effective and simple methods for obtaining them.Herein, we have reported a copper- and photoredox-catalyzed multicomponentreaction for 1,3-enynes, NH₄SCN, and NHPI esters, enablingthe efficient synthesis of propargyl thiocyanates. SET and EDA strategieswere applied. This novel method features redox-neutral conditions,wide substrate scope, and good functional group compatibility. Themechanistic experiment indicates that the reaction involves a radicalprocess.

Controlled condensed-state chemical reactions are criticalforsmart-material development. Reaction-driven self-assembly materialshave been explored for decades across organic nanostructure, polymer,and biomaterial research. This strategy has recently enabled the designand synthesis of nitrogen-rich hydrogen-bonded organic frameworksand size-matched hydrogen-bonded hydroxylammonium frameworks. Nevertheless,energetic-material research lacks reports on tuning self-assembledstructures of a single molecule via acid–base interactions.Herein, we present an acid–base-mediated, reaction-driven self-assemblystrategy to fabricate the high-energy-density metal–organicframework KADNPP (potassium 2-((7-amino-3,6-dinitro-5-oxo-4,5-dihydropyrazolo[1,5-a]pyrimidine-2-carbonyl)oxy)) and host–guest energeticmaterial HGEM-8. KADNPP displays an exceptionallyhigh measured density of 2.238 g cm^–3 and remarkablethermal stability (T_d = 376 °C).Meanwhile, HGEM-8 possesses a high density of 1.940 gcm^–3 (single crystal X-ray diffraction: 1.982 gcm^–3), excellent detonation performance (D = 9464 m s^–1; P = 43.5GPa), and superior solid-propellant performance (I_sp = 293 s, calculated by NASA CEA). These results demonstratethe significant potential of the present synthetic strategy for constructinghigh-energy-density self-assembled energetic materials.

Methylene and difluoromethyleneuridine bisphosphonate carbagalactosewere designed and synthesized as stable uridine diphosphate-galactose(UDP-Gal) mimics for probing α-1,4-galactosyltransferase (A4GALT).In these analogues, the labile glycosidic and pyrophosphate linkagesof UDP-Gal are replaced by chemically and enzymatically stable motifs,yielding compounds that retain key structural features essential forbiological recognition. This work demonstrates the first successfulnucleophilic substitution of a secondary triflate with a difluoromethylenebisphosphonate, providing a methodology that should enable efficientaccess to a range of sugar nucleotide mimics. The CH₂ andCF₂ UDP-Gal analogues 5 and 6 inhibited A4GALT, displaying IC₅₀ values of 249 and 217μM, respectively, in the presence of 500 μM UDP-Gal, consistentwith efficient recognition by the A4GALT donor-binding site.

A visible-light-driven one-pot decarboxylative cyclizationcascadevia an intramolecular electron donor–acceptor (EDA) complexis reported. By covalently tethering an indole donor and an NHPI esteracceptor with an alkyl linker, this strategy enables efficient assemblyof the signature 6/5/6/6 tetracyclic skeleton of corynanthe-type monoterpeneindole alkaloids under mild, metal- and photocatalyst-free neutralconditions. The transformation features a broad substrate scope (22examples), excellent yields (68–98%), and facile gram-scalescalability. Using this reaction as the key step, we achieved theenantioselective total synthesis of (+)-hirsutinol and (−)-dihydrocorynantheolin 8 linear steps, which represents, to the best of our knowledge,the first application of an intramolecular EDA strategy in the totalsynthesis of indole alkaloids.

Chiral 1,3-dioxygenated motifs are key scaffolds in bioactivenaturalproducts, yet their synthesis via intermolecular oxa-Michael additionto α,β-unsaturated aldehydes remains challenging notablydue to the high reversibility of the oxygenated nucleophile addition.This study presents a multicatalytic borrowing hydrogen (BH) strategycombining iridium-catalyzed reversible dehydrogenation/hydrogenationand enantioselective organocatalyzed iminium-type activation to overcomethese limitations. Under mild conditions (25°C), the approachenables the enantioselective oxa-Michael addition of oxygenated nucleophiles(oximes and alcohols) to allylic alcohols, directly delivering keyenantioenriched alcohols. Mechanistic studies confirm that the BHpathway displaces the equilibrium toward the alcohol product, limitingracemization at the aldehyde level occurring through rapid retro-oxa-Michaeladdition. This work demonstrates that BH catalysis can unlock otherwiseinaccessible transformations starting directly from aldehydes, offeringa sustainable and efficient route to complex chiral molecules.

Herein, we report the first nickel-catalyzed tandem dimerization/hydroheteroarylationof isoprenes with indoles, using a catalytic system consisting ofa heteroleptic Ni(II) complex Ni(IPr^*OMe)[P(OEt)₃]Br₂ and a base NaO^tBu. Thissystem provides easy access to a range of C2-substituted cyclic monoterpenoidindoles with high regioselectivity under solvent-free conditions.This tandem transformation shows good compatibility with indoles bearingvarious functional groups, such as esters, acetals, silanes, and boronateesters. The tandem transformation is also applicable to other heteroarenes,including pyrroles, (benzo)thiophenes, (benzo)furans, benzimidazoles,pyrazoles, quinazolones, imidazo[1,2-a]pyridines,and pyridines.

We report the synthesis of pseudo-herpotrichoneC and structure–activity relationship (SAR) studies of herpotrichone-basedanti-neuroinflammatory agents. A streamlined route employing methoxylativebromination and dual catalytic XAT-mediated elimination enabled accessto pseudo-herpotrichone C. SAR studies revealed thatC4–C19 stereochemistry, C16–C18 arrangement, and C3substitution of the herpotrichone framework collectively govern theneuroprotective activity. Notably, synthetic derivatives 4 and 5 inhibited LPS-induced nitric oxide productionmore strongly than natural herpotrichones A and B.