Zinc Promoted Cross-Electrophile Sulfonylation to Access Alkyl-Alkyl Sulfones.

The transition metal-catalyzed multi-component cross-electrophile sulfonylation, which incorporates SO2 as a linker within organic frameworks, has proven to be a powerful, efficient, and cost-effective means of synthesizing challenging alkyl-alkyl sulfones. Transition metal catalysts play a crucial role in this method by transferring electrons from reductants to electrophilic organohalides, thereby causing undesirable side reactions such as homocoupling, protodehalogenation, ß-hydride elimination, etc. It is worth noting that tertiary alkyl halides have rarely been demonstrated to be compatible with current methods owing to various undesired side reactions. In this work, a zinc-promoted cross-electrophile sulfonylation is developed through a radical-polar crossover pathway. This approach enables the synthesis of various alkyl-alkyl sulfones, including 1°-1°, 2°-1°, 3°-1°, 2°-2°, and 3°-2° types, from inexpensive and readily available alkyl halides. Various functional groups are well tolerated in the work, resulting in yields of up to 93%. Additionally, this protocol has been successfully applied to intramolecular sulfonylation and homo-sulfonylation reactions. The insights gained from this work shall be useful for the further development of cross-electrophile sulfonylation to access alkyl-alkyl sulfones.

Enhancing Hydride Transfer in Catalytic Hydrogenation via σ-Electron-Induced Polarization of Imines.

In this study, we investigated the role of aluminum cations in facilitating hydride transfer during the hydrogenation of imines within the context of Noyori-type metal-ligand cooperative catalysis. We propose a novel model involving aluminum cations directly coordinated with imines to induce activation from the lone pair electron site, a phenomenon termed σ-induced activation. The aluminum metal-hydride amidate complex ("HMn-NAl") exhibits a higher ability of hydride transfer in the hydrogenation of imines compared to its lithium counterpart ("HMn-NLi"). Density functional theory (DFT) calculations uncover that the aluminum cation efficiently polarizes unsaturated bonds through σ-electron-induced activation in the transition state of hydride transfer, thereby enhancing substrate electrophilicity more efficiently. Additionally, upon substrate coordination, aluminum's coordination saturation improves the hydride nucleophilicity of the HMn-NAl complex via the breakage of the Al-H coordination bond.

Overlooked interaction between redox-mediator and bisphenol-A in permanganate oxidation.

Research efforts on permanganate (Mn(VII)) combined with redox-mediator (RM), have received increasing attention due to their significant performance for bisphenol-A (BPA) removal. However, the mechanisms underpinning BPA degradation remain underexplored. Here we show the overlooked interactions between RM and BPA during permanganate oxidation by introducing an RM-N-hydroxyphthalimide (NHPI). We discovered that the concurrent generation of MnO2 and phthalimide-N-oxyl (PINO) radical significantly enhances BPA oxidation within the pH range of 5.0-6.0. The detection of radical cross-coupling products between PINO radicals and BPA or its derivatives corroborates the pivotal role of radical cross-coupling in BPA oxidation. Intriguingly, we observed the formation of an NHPI-BPA complex, which undergoes preferential oxidation by Mn(VII), marked by the emergence of an electron-rich domain in NHPI. These findings unveil the underlying mechanisms in the Mn(VII)/RM system and bridge the knowledge gap concerning BPA transformation via complexation. This research paves the way for further exploration into optimizing complexation sites and RM dosage, significantly enhancing the system's efficiency in water treatment applications.

Electrochemical Oxidation Enables Radical Dearomative Spiroannulation to 2H-Spiro[benzofuran-3,9'-fluoren]-2-one.

Developing pragmatic strategies for accessing functional benzofuran-2-ones from 3-([1,1'-biphenyl]-2-yl)benzofuran remains an enduring challenge. Herein, we have achieved a highly discriminating electrochemical oxidative dearomative spiroannulation of 3-([1,1'-biphenyl]-2-yl)benzofuran, culminating in the synthesis of 2H-spiro[benzofuran-3,9'-fluoren]-2-one derivatives. By harnessing the electrophilic intermediates of benzofuryl radical cations supported by DFT calculations, we attain exceptional regioselectivity while eliminating the need for stoichiometric oxidants. Mechanistic investigations reveal a sequence of events involving the benzofuran radical cation, encompassing the capture of H2O, nucleophilic arene attack, and subsequent deprotonation, ultimately yielding the final benzofuran-2-ones.

Rhodium-Catalyzed Direct ortho-Arylation of Anilines.

An efficient and broadly applicable rhodium-catalyzed direct ortho-arylation of anilines with aryl iodides relying on readily available aminophosphines as traceless directing groups is reported. Its scope and functional group compatibility were both found to be quite broad as a large variety of both aminophosphines and (hetero)aryl iodides, including complex ones, could be utilized. The ortho-arylated anilines could be obtained in high average yields, without any competing diarylation and with full regioselectivity, which constitutes a major step forward compared to other processes. The reaction is moreover not limited to aryl iodides, as an aryl bromide and a triflate could be successfully used, and could be extended to diarylation. Mechanistic studies revealed the key and unique role of the aminophosphine, acting not only as a substrate but also as a ligand for the rhodium catalyst.

Catalyst-Controlled Divergent Generations and Transformations of α-Carbonyl Cations from Alkynes.

α-Carbonyl cations are the umpolung forms of the synthetically fundamental α-carbonyl carbanions. They are highly reactive yet rarely studied and utilized species and their precursors were rather limited. Herein, we report the catalyst-controlled divergent generations of α-carbonyl cations from single alkyne functionalities and the interception of them via Wagner-Meerwein rearrangement. Two chemodivergent catalytic systems have been established, leading to two different types of α-carbonyl cations and, eventually, two different types of products, i.e. the α,ß- and ß,γ-unsaturated carbonyl compounds. Broad spectrum of alkynes including aryl alkyne, ynamide, alkynyl ether, and alkynyl sulfide could be utilized and the migration priorities of different groups in the Wagner-Meerwein rearrangement step was elucidated. Density functional theory calculations further supported the intermediacy of α-carbonyl cations via the N-O bond cleavage in both the two catalytic systems. Another key feature of this methodology was the fragmentation of synthetically inert tert-butyl groups into readily transformable olefin functionalities. The synthetic potential was highlighted by the scale-up reactions and the downstream diversifications including the formal synthesis of nicotlactone B and galbacin.

Valve turning towards on-cycle in cobalt-catalyzed Negishi-type cross-coupling.

Ligands and additives are often utilized to stabilize low-valent catalytic metal species experimentally, while their role in suppressing metal deposition has been less studied. Herein, an on-cycle mechanism is reported for CoCl2bpy2 catalyzed Negishi-type cross-coupling. A full catalytic cycle of this kind of reaction was elucidated by multiple spectroscopic studies. The solvent and ligand were found to be essential for the generation of catalytic active Co(I) species, among which acetonitrile and bipyridine ligand are resistant to the disproportionation events of Co(I). Investigations, based on Quick-X-Ray Absorption Fine Structure (Q-XAFS) spectroscopy, Electron Paramagnetic Resonance (EPR), IR allied with DFT calculations, allow comprehensive mechanistic insights that establish the structural information of the catalytic active cobalt species along with the whole catalytic Co(I)/Co(III) cycle. Moreover, the acetonitrile and bipyridine system can be further extended to the acylation, allylation, and benzylation of aryl zinc reagents, which present a broad substrate scope with a catalytic amount of Co salt. Overall, this work provides a basic mechanistic perspective for designing cobalt-catalyzed cross-coupling reactions.

Initiator-Activation Strategy-Enabled Organocatalyzed Reversible-Deactivation Radical Polymerization Driven by Light.

Organocatalyzed reversible-deactivation radical polymerizations (RDRPs) are attractive for many applications. Here, we developed photoredox-mediated RDRP by activating (hetero)aryl sulfonyl chloride (ArSO2 Cl) initiators with pyridines and designing a novel bis(phenothiazine)arene catalyst. The in situ formed sulfonyl pyridinium intermediates effectively promote controlled chain-growth from ArSO2 Cl, enabling access to various well-defined polymers with high initiation efficiencies and controlled dispersities under mild conditions. This versatile method allows "ON/OFF" temporal control, chain-extension, facile synthesis of different polymer brushes via organocatalyzed grafting reactions from linear chains. Time-resolved fluorescence decay studies and calculations support the reaction mechanism. This work provides a transition-metal-free RDRP to tailor polymers with readily available aromatic initiators, and will promote the design of polymerization leveraged from photoredox catalysis.

Revised Mechanism of C(sp3)-C(sp3) Reductive Elimination from Ni(II) with the Assistance of a Z-Type Metalloligand.

Reductive elimination is a key step in Ni-catalyzed cross-couplings. Compared with processes that proceed from Ni(III) or Ni(IV) intermediates, C(sp3)-C(sp3) reductive eliminations from Ni(II) centers are challenging due to the weak oxidizing ability of Ni(II) species. In this report, we present computational evidence that supports a mechanism in which Zn coordination to the nickel center as a Z-type ligand accelerates reductive elimination. This Zn-assisted pathway is found to be lower in energy compared with direct reductive elimination from a σ-coordinated Ni(II) intermediate, providing new insights into the mechanism of Ni-catalyzed cross-coupling with organozinc nucleophiles. Mayer bond order, Hirshfield charge, Laplacian of the electron density, orbital, and interaction region indicator analyses were conducted to elucidate details of the reductive elimination process and characterize the key intermediates. Theoretical calculations indicate a significant Z-type Ni-Zn interaction that reduces the electron density around the Ni center and accelerates reductive elimination. This mechanistic study of reductive elimination in Ni(0)-catalyzed conjunctive cross-couplings of aryl iodides, organozinc reagents, and alkenes is an important case study of the involvement of Zn-assisted reductive elimination in Ni catalysis. We anticipate that the novel Zn-assisted reductive elimination mode may extend to other cross-coupling processes and explain the unique effectiveness of organozinc nucleophiles in many instances.

How Strain-Release Determines Chemoselectivity: A Mechanistic Study of Rhodium-Catalyzed Bicyclo[1.1.0]butane Activation.

Bicyclo[1.1.0]butane (BCB) derivatives are versatile coupling partners, and various reaction modes for their activation and transformation have been proposed. In this work, three BCB-activation modes in Rh-catalyzed BCB transformations that construct diastereoselective α-quaternary ß-lactones were investigated by density functional theory calculations. Our results show that, compared with C1-C3 insertion and C-C3 oxidative addition, C2-C3 oxidative addition is more favorable. The whole catalytic cycle involves five main steps: C-H activation, oxidative addition, ß-C elimination/reductive elimination, Rh walking, and aldehyde insertion/protonation. Independent gradient model, intrinsic reaction coordinate, distortion-interaction energy, and Laplacian electron-density analyses were carried out to investigate the mode of BCB activation. Our calculation also showed that aldehyde-insertion is the diastereoselectivity determining step, which is controlled by the steric effect between the ligand, methyl group, and aldehyde.

Palladium-Catalyzed Intermolecular Asymmetric Dearomative Annulation of Phenols with Vinyl Cyclopropanes.

Herein, we report the Pd(0)-catalyzed intermolecular asymmetric dearomative [3 + 2] annulation of phenols with vinyl cyclopropanes via in situ generated ortho-quinone methide intermediates. A series of highly functionalized spiro-[5,6] bicycles which bear three contiguous stereogenic centers including one all-carbon quaternary were obtained with excellent stereoselectivities. Density functional theory (DFT) calculations indicate that the reactions were controlled by thermodynamics.

Regiospecific construction of m-alkenyl benzaldehyde from ß-bromoenal and vinyl borate.

Herein, we report a Pd-catalyzed regiospecific cycloaromatization of ß-bromoenal and vinyl borate esters to synthesize m-alkenyl substituted benzaldehydes. This allows the construction of complex molecules from simple materials, which may be useful in the search for new optical materials.

Oxymetalation or oxidative cyclization? mechanism of Pd-catalyzed annulation of enynones.

Enynones are powerful synthons for constructing furan derivatives in the presence of transition metal catalysts. Unlike the conventional intramolecular nucleophilic attack with the activation of coinage metals, we propose that enynones undergo an oxidative cyclization process with a Pd(0) species. The full catalytic cycle involves oxidative cyclization, isocyanide insertion, and reductive elimination, which was supported by DFT calculations. Geometric and electronic analyses confirmed the oxidative cyclization process, which proceeds via a Pd(ii) intermediate.

Role of TEMPO in Enhancing Permanganate Oxidation toward Organic Contaminants.

Permanganate (Mn(VII)) has been widely applied as an oxidant in water treatment plants. However, compared with ozone, Fenton, and other advanced oxidation processes, the reaction rates of some trace organic contaminants (TrOCs) with Mn(VII) are relatively low. Therefore, further studies on the strategies for enhancing the oxidation of organic contaminants by Mn(VII) are valuable. In this work, 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), as an electron shuttle, enhanced Mn(VII) oxidation toward various TrOCs (i.e., bisphenol A (BPA), phenol, estrone, sulfisoxazole, etc.). TEMPO sped up the oxidative kinetics of BPA by Mn(VII) greatly, and this enhancement was observed at a wide pH range of 4.0-11.0. The exact mechanism of TEMPO in Mn(VII) oxidation was described briefly as follows: (i) TEMPO was oxidized by Mn(VII) to its oxoammonium cation (TEMPO+) by electron transfer, which was the reactive species responsible for the accelerated degradation of TrOCs and (ii) TEMPO+ could decompose TrOCs rapidly with itself back to TEMPO or TEMPOH (TEMPO hydroxylamine). To further illustrate the interaction between TEMPO and target TrOCs, we explored the transformation pathways of BPA in Mn(VII)/TEMPO oxidation. Compared to Mn(VII) alone, adding TEMPO into the Mn(VII) solution significantly suppressed BPA's self-coupling and promoted hydroxylation, ring-opening, and decarboxylation. Moreover, the Mn(VII)/TEMPO system was promising for the abatement of TrOCs in real waters for humic acid, and ubiquitous cations/anions had no adverse or even beneficial impact on the Mn(VII)/TEMPO system.

How Solvents Control the Chemoselectivity in Rh-Catalyzed Defluorinated [4 + 1] Annulation.

Density functional theory calculations have been performed to reveal the chemoselectivity of Rh-catalyzed chiral C-F cleavage and γ-site functionalization. We found that the chemoselectivity is controlled by ß-F elimination in methanol solvent, leading to formation of the alkynylic product. In isobutyronitrile solvent, the chemoselectivity is controlled by the allene insertion step, where the fluoroalkenylic product can be observed. The difference can be explained by analysis of the explicit solvent models.

Nickel-Catalyzed C-F/N-H Annulation of Aromatic Amides with Alkynes: Activation of C-F Bonds under Mild Reaction Conditions.

The Ni-catalyzed reaction of ortho-fluoro-substituted aromatic amides with alkynes results in C-F/N-H annulation to give 1(2H)-isoquinolinones. A key to the success of the reaction is the use of KOtBu or even weak base, such as Cs2CO3. The reaction proceeds in the absence of a ligand and under mild reaction conditions (40-60 °C). DFT calculations suggest that the pathway for this Ni-catalyzed C-F/N-H annulation involves N-H deprotonation, oxidative addition of a C-F bond, migratory insertion of an alkyne, and reductive elimination to form 1(2H)-isoquinolinone derivatives.

Layered Chirality Relay Model in Rh(I)-Mediated Enantioselective C-Si Bond Activation: A Theoretical Study.

A three-layer chirality relay model is proposed for Rh(I)-mediated enantioselective siletane activation. A chiral ligand in the back layer controls the position of the alkyne-coordinated metal center in the middle layer, which then provides a chiral environment for the incoming substrate at the front layer. A two-dimensional contour map analysis further clarified this model.

Reaction scope and mechanistic insights of nickel-catalyzed migratory Suzuki-Miyaura cross-coupling.

Cross-coupling reactions have developed into powerful approaches for carbon-carbon bond formation. In this work, a Ni-catalyzed migratory Suzuki-Miyaura cross-coupling featuring high benzylic or allylic selectivity has been developed. With this method, unactivated alkyl electrophiles and aryl or vinyl boronic acids can be efficiently transferred to diarylalkane or allylbenzene derivatives under mild conditions. Importantly, unactivated alkyl chlorides can also be successfully used as the coupling partners. To demonstrate the applicability of this method, we showcase that this strategy can serve as a platform for the synthesis of terminal, partially deuterium-labeled molecules from readily accessible starting materials. Experimental studies suggest that migratory cross-coupling products are generated from Ni(0/II) catalytic cycle. Theoretical calculations indicate that the chain-walking occurs at a neutral nickel complex rather than a cationic one. In addition, the original-site cross-coupling products can be obtained by alternating the ligand, wherein the formation of the products has been rationalized by a radical chain process.

Enhanced Transformation of Emerging Contaminants by Permanganate in the Presence of Redox Mediators.

In this study, a permanganate/redox mediator system for enhanced transformation of a series of emerging contaminants was evaluated. The presence of various redox mediators (i.e., 1-hydroxybenzotriazole, N-hydroxyphthalimide, violuric acid, syringaldehyde, vanillin, 4-hydroxycoumarin, and p-coumaric acid) accelerated the degradation of bisphenol A (BPA) by Mn(VII). Since 1-hydroxybenzotriazole (HBT) exhibited the highest reactive ability, it was selected to further investigate the reaction mechanisms and quantify the effects of important reaction parameters on Mn(VII)/redox-mediator reactions with BPA and bisphenol AF (BPAF). Interestingly, not only HBT accelerated the degradation of BPA, but also BPA enhanced the decay of HBT. Evidence for the in situ formation of HBT· radicals as the active oxidant responsible for accelerated BPA and BPAF degradation was obtained by radical scavenging experiments and 31P NMR spin trapping techniques. The routes for HBT· radical formation involving Mn(VII) and the electron-transfer pathway from BPA/BPAF to HBT· radicals demonstrate that the Mn(VII)/HBT system was driven by the electron-transfer mechanism. Compared to Mn(VII) alone, the presence of HBT totally inhibited self-coupling of BPA and BPAF and promoted ß-scission, hydroxylation, ring opening, and decarboxylation reactions. Moreover, Mn(VII)/HBT is also effective in real waters with the order of river water > wastewater treatment plant (WWTP) effluent > deionized water.

Hydrogen-Bond-Induced Chiral Axis Construction: Theoretical Study of Cinchonine-Thiourea-Catalyzed Enantioselective Intramolecular Cycloaddition.

Theoretical calculations were performed to investigate the mechanism and enantioselectivity of cinchonine-thiourea-catalyzed intramolecular hetero-Diels-Alder cycloaddition of ethynylphenol derivatives to afford axial chirality naphthalenylpyran products via a vinylidene ortho-quinone methide (VQM) intermediate. The results show that this transformation occurs through a reaction pathway involving the deprotonation of the naphthol moiety by the quinuclidine base, intramolecular proton transfer in ammonium naphthalenolate, and [4+2] cycloaddition. It is found that the axial chirality of the VQM intermediate is generated by the protonation step, which affects the enantioselectivity of the reaction. The enantioselectivity for the generation of the VQM intermediate is controlled by steric repulsion with the cinchonine framework, which provides an R-axial chirality VQM as the major intermediate. Moreover, the enantioselectivity for the axial chirality of the naphthopyran product is controlled by the cycloaddition step, in which an extra hydrogen bond between the naphthalenol and cinchonine moieties leads to a favorable configuration for the generation of the S-axial chirality naphthopyran product. The calculated enantioselectivity and enantiomeric excesses coincide with experimental observations.