Iron-Mediated Dialkylation of Alkenylarenes with Benzyl Bromides.

We disclose a method for the dibenzylation of alkenylarenes with benzyl bromides using iron powder. This reaction generates branched alkyl scaffolds adorned with functionalized aryl rings through the formation of two new C(sp3)-C(sp3) bonds at the vicinal carbons of alkenes. This protocol tolerates electron-rich, electron-neutral, and electron-poor benzyl bromides and alkenylarenes. Mechanistic studies suggest the formation of benzylic radical intermediates as a result of single-electron transfer from the iron, which is intercepted by alkenylarenes.

Pd-Catalyzed 1,3-Alkenylarylation of Skipped Diene via Metal Migration.

We disclose a palladium-catalyzed difunctionalization of skipped diene with alkenyl triflates and arylboronic acids to produce 1,3-alkenylarylated products. The reaction proceeded efficiently with Pd(acac)2 as a catalyst and CsF as a base for a wide range of electron-deficient and electron-rich arylboronic acids as well as oxygen-heterocyclic, sterically hindered, and complex natural product-derived alkenyl triflates bearing various functional groups. The reaction produced 3-aryl-5-alkenylcyclohexene derivatives with 1,3-syn-disubstituted stereochemistry.

Cu-Catalyzed Cyclization/Coupling of Alkenyl Aldimines with Arylzinc Reagents: Access to Indole-3-diarylmethanes.

We report a Cu(II)-catalyzed cyclization/coupling of alkenyl aldimines with arylzinc reagents to create indole-3-diarylmethane derivatives (Sapkota et al. ChemRxiv 2022, DOI: 10.26434/chemrxiv-2022-d6qn). The current reaction provides a unified modular route from readily available starting materials to indole-3-diarylmethanes in which all three arene cores can be decorated with differential functional substitutions on demand. Since the cyclization/coupling of alkenyl aldimines is unknown to date, the current method widens the scope with regard to both the substrate and product diversity for this class of reaction.

Ni-Catalyzed Regio- and Stereoselective Alkylarylation of Unactivated Alkenes in γ,δ-Alkenylketimines.

We disclose a Ni-catalyzed vicinal alkylarylation of unactivated alkenes in γ,δ-alkenylketimines with aryl halides and alkylzinc reagents. The reaction produces γ-C(sp3)-branched δ-arylketones with the construction of two new C(sp3)-C(sp3) and C(sp3)-C(sp2) bonds. Electron-deficient alkenes play crucial dual roles as ligands to stabilize reaction intermediates and to increase catalytic rates for the formation of C(sp3)-C(sp3) bonds. This alkene alkylarylation reaction is also effective for secondary alkylzinc reagents and internal alkenes, and proceeds with a complete regio- and stereocontrol, affording products with up to three contiguous all-carbon all-cis secondary stereocenters.

Ni-Catalyzed Arylbenzylation of Alkenylarenes: Kinetic Studies Reveal Autocatalysis by ZnX2 *.

We report a Ni-catalyzed regioselective arylbenzylation of alkenylarenes with benzyl halides and arylzinc reagents. The reaction furnishes differently substituted 1,1,3-triarylpropyl structures that are reminiscent of the cores of oligoresveratrol natural products. The reaction is also compatible for the coupling of internal alkenes, secondary benzyl halides and variously substituted arylzinc reagents. Kinetic studies reveal that the reaction proceeds with a rate-limiting single-electron-transfer process and is autocatalyzed by in-situ-generated ZnX2 . The reaction rate is amplified by a factor of three through autocatalysis upon addition of ZnX2 .

Nickel-Catalyzed Regioselective Alkenylarylation of γ,δ-Alkenyl Ketones via Carbonyl Coordination.

We disclose a nickel-catalyzed reaction, which enabled us to difunctionalize unactivated γ,δ-alkenes in ketones with alkenyl triflates and arylboronic esters. The reaction was made feasible by the use of 5-chloro-8-hydroxyquinoline as a ligand along with NiBr2 ⋅DME as a catalyst and LiOtBu as base. The reaction proceeded with a wide range of cyclic, acyclic, endocyclic and exocyclic alkenyl ketones, and electron-rich and electron-deficient arylboronate esters. The reaction also worked with both cyclic and acyclic alkenyl triflates. Control experiments indicate that carbonyl coordination is required for the reaction to proceed.

Ni-Catalyzed Regioselective 1,2-Dialkylation of Alkenes Enabled by the Formation of Two C(sp3)-C(sp3) Bonds.

We disclose a Ni-catalyzed vicinal difunctionalization of alkenes with benzyl halides and alkylzinc reagents, which produces products with two new alkyl-alkyl bonds. This alkene dialkylation is effective in combining secondary benzyl halides and secondary alkylzinc reagents with internal alkenes, which furnishes products with three contiguous all-carbon secondary stereocenters. The products can be readily elaborated to access complex tetralene, benzosuberene, and bicyclodecene cores. The reaction also features as the most efficient alkene difunctionalization process to date with catalyst loadings down to 500 ppm and the catalytic turnover number (TON) and turnover frequency (TOF) registering up to 2 × 103 and 165 h-1 at rt, respectively.

K2CO3-Catalyzed Synthesis of 2,5-Dialkyl-4,6,7-tricyano-Decorated Indoles via Carbon-Carbon Bond Cleavage.

We describe a novel method to synthesize 2,5-dialkyl-4,6,7-tricyanoindole derivatives from a base-catalyzed reaction of 1,3-diketones with fumaronitrile. The reaction proceeds by the condensation of two molecules of fumaronitrile and one molecule of 1,3-diketone in a remarkable process that involves the cleavage of one C(sp3)-C(sp2) bond in 1,3-diketones and the formation of one carbon-nitrogen bond and four carbon-carbon bonds to construct both the aryl and pyrrole rings of the indole in one step.

An Expedient Route to 9-arylmethylanthracene Derivatives via Tandem Ni-catalyzed Alkene Dicarbofunctionalization and Acid-promoted Cyclization-aromatization.

We report a nickel-catalyzed one pot synthesis of 9-arylmethylanthracene motifs, which find applications in medicinal and material chemistry. In this synthesis, we apply three component alkene dicarbofunctionalization of 2-vinylaldimines with aryl iodides and arylzinc reagent to generate a 1,1,2-diarylethyl scaffold, which then undergoes an acidpromoted cyclization followed by aromatization to furnish 9-arylmethylanthracene cores. With the new method, a number of differently-substituted 9-arylmethylanthracene derivatives can be synthesized in good yields.

Walking metals: catalytic difunctionalization of alkenes at nonclassical sites.

Migration of metals along a carbon chain is triggered by two of the most common organometallic elementary steps - ß-hydride (ß-H) elimination and alkene hydrometallation. This process heralds a new future for creating bonds at carbon sites that fall outside the tenets of the conventional wisdom for reactivity and bond formation, and provides an opportunity to leverage ß-H elimination to advance the very reaction of alkene difunctionalization it is intrinsically predestined to disrupt. Almost four decades since its genesis, the early adventure for alkene difunctionalization by metal migration was sporadic, and its later development went on a hiatus primarily due to original impetus on arresting ß-H elimination for vicinal alkene difunctionalization. With the recent surge on alkene difunctionalization, efforts have been gradually shifting to harnessing the process of ß-H elimination to difunctionalize alkenes at sites other than the classical vicinal carbons, termed henceforth nonclassical reaction sites for pedagogical simplicity. In this review article, we extricate and examine the origin and the development of such reactions over the years. This review covers a wide range of reactions for the difunctionalization of alkenes at geminal (1,1), allylic (1,3) and remote (1,n) carbon sites with a variety of coupling partners. These reactions have enabled engineering of complex molecular frameworks with the generation of new carbon-carbon (C-C)/C-C, C-C/C-heteroatom (halogens, O, N, B) and C-B/C-B bonds. The development of these unique transformations is also presented with mechanistic hypotheses and experimental evidences put forward by researchers. Judged by the number of reports emerging recently, it is now strikingly evident that the field of alkene difunctionalization by metal migration has begun to gain momentum, which holds a great future prospect to develop into a synthetic method of enormous potential.

Bimolecular Cross-Metathesis of a Tetrasubstituted Alkene with Allylic Sulfones.

Exquisite control of catalytic metathesis reactivity is possible through ligand-based variation of ruthenium carbene complexes. Sterically hindered alkenes, however, remain a generally recalcitrant class of substrates for intermolecular cross-metathesis. Allylic chalcogenides (sulfides and selenides) have emerged as "privileged" substrates that exhibit enhanced turnover rates with the commercially available second-generation ruthenium catalyst. Increased turnover rates are advantageous when competing catalyst degradation is limiting, although specific mechanisms have not been defined. Herein, we describe facile cross-metathesis of allylic sulfone reagents with sterically hindered isoprenoid alkene substrates. Furthermore, we demonstrate the first example of intermolecular cross-metathesis of ruthenium carbenes with a tetrasubstituted alkene. Computational analysis by combined coupled cluster/DFT calculations exposes a favorable energetic profile for metallacyclobutane formation from chelating ruthenium ß-chalcogenide carbene intermediates. These results establish allylic sulfones as privileged reagents for a substrate-based strategy of cross-metathesis derivatization.

Adsorption and photocatalytic oxidation of ibuprofen using nanocomposites of TiO2 nanofibers combined with BN nanosheets: Degradation products and mechanisms.

This study investigated the adsorption and photocatalytic activity of titanium dioxide (TiO2)-boron nitride (BN) nanocomposites for the removal of contaminants of emerging concern in water using ibuprofen as a model compound. TiO2 nanofibers wrapped by BN nanosheets were synthesized by electrospinning method. Characterization of the nanocomposite photocatalysts indicated that the BN nanosheets improved the light absorbance and reduced the recombination of the photoexcited charge carriers (e- and h+). The photocatalytic oxidation products and mechanisms of ibuprofen by the TiO2-BN catalysts were elucidated using a multiple analysis approach by high performance liquid chromatography, ultraviolet absorbance, dissolved organic carbon, fluorescence excitation-emission matrices, and electrospray ionization-liquid chromatography-tandem mass spectrometry. The experimental results revealed that the photocatalytic oxidation by the TiO2-BN nanocomposites is a multi-step process and the interactions between ibuprofen molecules and the TiO2-BN nanocomposites govern the adsorption process. The increasing BN nanosheet content in the TiO2 nanofibers facilitated the breakdown of ibuprofen degradation intermediates (hydroxyibuprofen, carboxyibuprofen, and oxypropyl ibuprofen). Kinetic modeling indicated both adsorption and photocatalytic oxidation of ibuprofen by the TiO2-BN nanocomposites followed the first-order kinetic model. The photocatalytic oxidation rate increased with the increasing BN content in the nanocomposite catalysts, which was attributed to the enhanced light absorption capacity and the separation efficiency of the photoexcited electron (e-)-hole (h+) pairs. Multiple photocatalytic cycles were conducted to investigate the reusability and regeneration of the nanofibers for ibuprofen degradation.

Lewis-Acid-Mediated Union of Epoxy-Carvone Diastereomers with Anisole Derivatives: Mechanistic Insight and Application to the Synthesis of Non-natural CBD Analogues.

The use of trimethylsilyl trifluoromethanesulfonate as a mild means to unite epoxy-carvone silyl ethers with anisole derivatives to yield products that are structurally similar to the CBD scaffold is reported. Importantly, unlike related methods, this process can utilize both epoxy-carvone diastereomers and does not require the use of air/moisture-sensitive organometallic reagents. Several examples of aryl nucleophiles as well as mechanistic insight based on in silico computational analysis are presented.