Pinacol Rearrangement Research Articles

Synthesis of 1-Substituted Bicyclo[2.1.1]hexan-2-ones via a Sequential SmI2-Mediated Pinacol Coupling and Acid-Catalyzed Pinacol Rearrangement Reaction.

A two-step procedure, combining a SmI2-mediated transannular pinacol coupling reaction with an acid-catalyzed pinacol rearrangement process, was employed to prepare a diverse range of 1-substituted bicyclo[2.1.1]hexan-5-ones from cyclobutanedione derivatives. To underscore the significance of these bicyclic ketones in drug synthesis, an sp3-rich analog of nitazoxanide, a well-known antiparasitic and antiviral agent, was synthesized.

Acceptorless Dehydrogenation of Alcohols and Polyols Over Cu‐Based Catalysts Prepared by NaBH4 Reduction

AbstractFor the first time, oxide (TiO2, CeO2, ZnO, Al2O3) supported Cu catalysts, prepared by the aqueous reduction method using sodium borohydride, were employed for the acceptorless dehydrogenation of 2‐octanol and various C4–C8 polyols. The method used to prepare the catalysts enabled the formation of small Cu particles in the range of 14–36 nm, depending on the point of the zero charge of the support. We showed that the conversion increased with Cu surface area, where Cu/TiO2 led to the highest conversion of 2‐octanol (>99.9%). The selectivity depends on the support and conversion. Up to 80% conversion, the selectivity to 2‐octanone was between 83% and 90% when using Cu/TiO2. In this study, we also report for the first time the acceptorless dehydrogenation of 1,3‐butanediol, 2,3‐butanediol, 1,2‐pentanediol, and 1,5‐pentanediol in liquid phase. While metal active sites promoted the dehydrogenation reaction, the presence of acidic and basic sites favored the formation of by‐products, mainly resulting from dehydration reactions, pinacol rearrangements, and aldol and retro‐aldol condensations. In addition to value‐added chemicals, all the reactions also released molecular hydrogen.

Structural determination of a carbocation-derived rearrangement product observed during Thiele cage opening: insight into the mechanism of an alkyl-extended pinacol reaction

A substituted bishomocubane structure colloquially known as a Thiele cage was previously observed to undergo an alkyl-extended pinacol-type rearrangement, wherein 1,2-aryl migration and ketone formation occurred together with (or at least in close succession to) opening of a strained cyclobutane bond. While there was some indication that the rearrangement reaction might proceed via a stepwise process involving a sequence of carbocation intermediates, previous studies did not uncover any direct evidence for the formation of carbocations, and did not fully explain the regio- and stereospecificity of the reaction. Here we describe the isolation and detailed characterization of a second rearrangement product formed under the pinacol reaction conditions, the existence of which implicates the formation of discrete carbocation intermediates along the reaction pathway. Observation of this new product also finally explains the fate of any Thiele cage material that is converted to a carbocation, but which is not geometrically predisposed to react through a facile 1,2-aryl migration. As such, our findings resolve previous questions surrounding the origin of regio- and stereospecificity in the alkyl-extended pinacol rearrangement.

Highly Efficient One-Pot Synthesis of 2,4,5-Trisubstituted 3(2H)-Furanones Utilizing a Au(I)-Catalyzed Oxidation/Pinacol Rearrangement/anti-Michael Cascade.

A highly efficient Au(I)-catalyzed cascade reaction between bispropargylic alcohols and pyridine-N-oxides has been realized. The reaction process involved a gold(I)-catalyzed sequential oxidation/Pinacol rearrangement/oxacyclization. Moreover, 1,2-aryl, 1,2-alkyl, or 1,2-vinyl migration was favored over 1,2-alkynyl in the crucial gold(I)-catalyzed Pinacol rearrangement step. A range of 2,4,5-trisubstituted 3(2H)-furanones were synthesized in high yields (up to 88%) with excellent regioselectivities (up to >19:1) under mild reaction conditions.

Silica-Ti3C2Tx MXene Nanoarchitectures with Simultaneous Adsorption and Photothermal Properties.

Layered Ti3C2Tx MXene has been successfully intercalated and exfoliated with the simultaneous generation of a 3D silica network by treating its cationic surfactant intercalation compound (MXene-CTAB) with an alkoxysilane (TMOS), resulting in a MXene-silica nanoarchitecture, which has high porosity and specific surface area, together with the intrinsic properties of MXene (e.g., photothermal response). The ability of these innovative MXene silica materials to induce thermal activation reactions of previously adsorbed compounds is demonstrated here using NIR laser irradiation. For this purpose, the pinacol rearrangement reaction has been selected as a first model example, testing the effectiveness of NIR laser-assisted photothermal irradiation in these processes. This work shows that Ti3C2Tx-based nanoarchitectures open new avenues for applications that rely on the combined properties inherent to their integrated nanocomponents, which could be extended to the broader MXene family.

Acid-Catalytic Effect of Alcohol Dissociation on Pinacol Rearrangement in Hot Compressed Water

Acid-Catalytic Effect of Alcohol Dissociation on Pinacol Rearrangement in Hot Compressed Water

Discovery of Antibacterial Compounds against Xanthomonas citri subsp. citri from a Marine Fungus Aspergillus terreus SCSIO 41202 and the Mode of Action.

Citrus canker, caused by Xanthomonas citri subsp. citri (Xcc), is a severe citrus disease. Currently, copper-containing pesticides are widely used to manage this disease, posing high risks to the environment and human health. This study reports the discovery of naturally occurring anti-Xcc compounds from a deep-sea fungus, Aspergillus terreus SCSIO 41202, and the possible mode of action. The ethyl acetate extract of A. terreus was subjected to bioassay-guided isolation, resulting in the discovery of eight anti-Xcc compounds (1-8) with minimum inhibitory concentrations (MICs) ranging from 0.078 to 0.625 mg/mL. The chemical structures of these eight metabolites were determined by integrative analysis of various spectroscopic data. Among these compounds, Asperporonin A (1) and Asperporonin B (2) were identified as novel compounds with a very unusual structural skeleton. The electronic circular dichroism was used to determine the absolute configurations of 1 and 2 through quantum chemical calculation. A bioconversion pathway involving pinacol rearrangement was proposed to produce the unusual compounds (1-2). Compound 6 exhibited an excellent anti-Xcc effect with a MIC value of 0.078 mg/mL, which was significantly more potent than the positive control CuSO4 (MIC = 0.3125 mg/mL). Compound 6 inhibited cell growth by disrupting biofilm formation, destroying the cell membrane, and inducing the accumulation of reactive oxygen species. In vivo tests indicated that compound 6 is highly effective in controlling citrus canker disease. These results indicate that compounds 1-8, especially 6, have the potential as lead compounds for the development of new, environmentally friendly, and efficient anti-Xcc pesticides.

Microwave pyrolysis of sewage sludge for bio-oil production: Effects of organic components and mechanisms

The microwave pyrolysis (MWP) of sewage sludge (SS) was conducted to investigate the impact of the organic composition of SS on the yield and composition of the derived bio-oil. The experiments were conducted in a microwave oven at 900 °C with a heating rate of 50 °C/min and achieved the product yield of 43.10 ± 2.23% bio-oil, 48.07 ± 1.26% bio-char, 8.83 ± 1.65% bio-gas. The chemical composition of bio-oil was investigated using gas chromatography–mass spectrometry and 145 species were identified. Protein and lipid contents in SS are the primary source of bio-oil yield, while bio-gas are predominantly derived from lignocellulosic materials. The unique non-thermal effects of microwaves can facilitate the ring-opening of small cycloalkanes to form straight olefins through hydrogen transfer reactions. Additionally, they can promote aldol condensation reactions, Pinacol rearrangements, and methoxy cleavage to form phenolic and aromatic structures with methyl groups. Furthermore, microwaves can aid in the dehydration, condensation, and cyclization reactions of amino acids to produce N-heterocycles while also facilitating lipid depolymerization into fragments for Diels–Alder cyclization. The results of this study will be beneficial for deeply understanding reactant characteristics and the reaction process during the MWP of SS.

Synthesis of Bicyclo[2.1.1]hexan‐5‐ones via a Sequential Simmons‐Smith Cyclopropanation and an Acid‐Catalyzed Pinacol Rearrangement of α‐Hydroxy Silyl Enol Ethers

AbstractA synthetic strategy involving a Simmons‐Smith cyclopropanation, followed by an acid‐catalyzed pinacol rearrangement, was developed to transform α‐hydroxy silyl enol ethers into 1‐substituted bicyclo[2.1.1]hexan‐5‐ones. These bicyclic ketones underwent further synthetic manipulations to generate various 1,5‐disubstituted bicyclo[2.1.1]hexanes, which could serve as potential bioisosteres of ortho‐substituted arenes.

Advances and Perspectives in Pinacol Rearrangement Reactions: A Comprehensive Review

Advances and Perspectives in Pinacol Rearrangement Reactions: A Comprehensive Review

Degradation Profiling of Nardosinone at High Temperature and in Simulated Gastric and Intestinal Fluids.

Nardosinone, a predominant bioactive product from Nardostachys jatamansi DC, is well-known for its promising therapeutic applications, such as being used as a drug on anti-inflammatory, antidepressant, cardioprotective, anti-neuroinflammatory, anti-arrhythmic, anti-periodontitis, etc. However, its stability under varying environmental conditions and its degradation products remain unclear. In this study, four main degradation products, including two previously undescribed compounds [2-deoxokanshone M (64.23%) and 2-deoxokanshone L (1.10%)] and two known compounds [desoxo-narchinol A (2.17%) and isonardosinone (3.44%)], were firstly afforded from the refluxed products of nardosinone in boiling water; their structures were identified using an analysis of the extensive NMR and X-ray diffraction data and the simulation and comparison of electronic circular dichroism spectra. Compared with nardosinone, 2-deoxokanshone M exhibited potent vasodilatory activity without any of the significant anti-neuroinflammatory activity that nardosinone contains. Secondly, UPLC-PDA and UHPLC-DAD/Q-TOF MS analyses on the degradation patterns of nardosinone revealed that nardosinone degraded more easily under high temperatures and in simulated gastric fluid compared with the simulated intestinal fluid. A plausible degradation pathway of nardosinone was finally proposed using nardosinonediol as the initial intermediate and involved multiple chemical reactions, including peroxy ring-opening, keto-enol tautomerization, oxidation, isopropyl cleavage, and pinacol rearrangement. Our findings may supply certain guidance and scientific evidence for the quality control and reasonable application of nardosinone-related products.

Electroreductive Coupling of Aldehydes and Subsequent Pinacol Rearrangement for 1,2‐Disubstituted Ethanones

AbstractAn electrochemical method for the generation of 1,2‐diols through the reductive coupling of aldehydes has been developed, and the 1,2‐diols were used directly without separation for the pinacol rearrangement process. The electro‐organic strategy had mild reaction conditions and avoided the use of reductants. The pinacol rearrangement was controllable to access to the hydride‐migrated product 1,2‐disubstituted. The key factor in selectivity was the use of macrocyclic compound cucurbit[7]uril, which plays a key role in the interaction with aromatic ring of 1,2‐diol. On the basis of experimental results, the mechanism, include the electroreductive coupling and pinacol rearrangement process, was illustrated.

Collective Total Synthesis of Mavacuran Alkaloids through Intermolecular 1,4‐Addition of an Organolithium Reagent**

AbstractWe report a synthetic endeavor towards the highly strained pentacyclic caged framework of the mavacuran alkaloids which culminated with the concise total synthesis of C‐fluorocurine, C‐profluorocurine, C‐mavacurine, normavacurine, 16‐epi‐pleiocarpamine and taberdivarine H. We designed a strategy involving late‐stage construction of the D ring by Michael addition of a vinylic nucleophile to a 2‐indolyl acrylate moiety. While the intramolecular Michael addition did not succeed, we were able to perform a diastereoselective unusual intermolecular 1,4‐addition of a functionalized vinyl lithium reagent to a readily accessible Michael acceptor with the assistance of the piperidine nitrogen atom through the formation of a complex as suggested by DFT computations. Final cyclization was achieved by nucleophilic substitution to form an ammonium intermediate. The first total syntheses of C‐profluorocurine and C‐fluorocurine were finalized by the dihydroxylation of C‐mavacurine and a pinacol rearrangement, respectively.

Collective Total Synthesis of Mavacuran Alkaloids through Intermolecular 1,4-Addition of an Organolithium Reagent.

We report a synthetic endeavor towards the highly strained pentacyclic caged framework of the mavacuran alkaloids which culminated with the concise total synthesis of C-fluorocurine, C-profluorocurine, C-mavacurine, normavacurine, 16-epi-pleiocarpamine and taberdivarine H. We designed a strategy involving late-stage construction of the D ring by Michael addition of a vinylic nucleophile to a 2-indolyl acrylate moiety. While the intramolecular Michael addition did not succeed, we were able to perform a diastereoselective unusual intermolecular 1,4-addition of a functionalized vinyl lithium reagent to a readily accessible Michael acceptor with the assistance of the piperidine nitrogen atom through the formation of a complex as suggested by DFT computations. Final cyclization was achieved by nucleophilic substitution to form an ammonium intermediate. The first total syntheses of C-profluorocurine and C-fluorocurine were finalized by the dihydroxylation of C-mavacurine and a pinacol rearrangement, respectively.

Predictable incorporation of nitrogen into carbon dots: insights from pinacol rearrangement and iminium ion cyclization.

Nitrogen-doped carbon dots (CDs) have attracted considerable attention across various research areas and applications due to their enhanced optical properties and photostability. However, the mechanism of nitrogen incorporation in CDs remains elusive, hampering the precise control over nitrogen-incorporated structures and the investigation of the effects of nitrogen on the electronic structure and optical properties of CDs. In this study, we employed a rational design approach, utilizing glucosamine and ethylene glycol as the carbon source and co-reagent, respectively, to synthesize N-doped CDs. Our synthesis strategy involved pinacol rearrangement and iminium ion cyclization reactions, enabling the reliable formation of N-doped CDs. Notably, the resulting CDs exhibited distinctive emissive states attributed to heteroatomic defect structures, including oxygenic and nitrogenic polycyclic aromatic hydrocarbons. To gain further insights into their energy levels and electronic transitions, we conducted comprehensive investigations, employing extended Hückel calculations and pump-probe spectroscopy. The synthesized CDs displayed great promise as bioimaging and photodynamic therapy agents, highlighting their potential for biomedical applications. Moreover, our study significantly contributes valuable insights into the rational design of N-doped CDs with controllable chemical and electronic structures, thereby paving the way for advancements in their diverse range of applications.

Investigation into the Mechanism and Migratory Aptitude of Typical Pinacol Rearrangement Reactions: A Research-Oriented Computational Chemistry Experiment

Investigation into the Mechanism and Migratory Aptitude of Typical Pinacol Rearrangement Reactions: A Research-Oriented Computational Chemistry Experiment

Recent Advances in Pinacol Rearrangement

Abstract: A pinacol rearrangement is a well-known reaction by which a 1,2-diol is converted to a carbonyl compound through acid-catalyzed dehydration followed by a 1,2-migration of one of the neighboring substituents. Due to the particular abilities in installing polycyclic skeletons, quaternary carbon centers, and spirocyclic cores, the pinacol rearrangement reaction is a powerful and effective means of forming carbonyl functional groups in a variety of different molecules. Moreover, the substrates with an alkene group, a furan ring or alkyl chain tethered between the two diols have also been investigated as the expansion of pinacol rearrangement. Benefiting from the continuous development of the catalysis methodologies, pinacol rearrangements demonstrate synthetic utility in the preparation of natural products, bioactive molecules, and other functionally useful compounds. In this review, we discuss recent advances in the development of pinacol rearrangement and extended pinacol rearrangement reactions catalyzed by Brønsted acid, Lewis acid, and heterogeneous catalysts. In addition, we summarize several examples use pinacol rearrangements used in the synthesis of natural products and other valuable molecules.

Cucurbit[7]uril‐Catalyzed Controllable Pinacol Rearrangement with Activated Hydride Migration

AbstractA selective pinacol rearrangement of hydrobenzoin compounds was established through a heterogeneous catalysis strategy in the presence of cucurbit[7]uril. As an unexpected consequence, the ketone was generated as the sole product with the cucurbit[7]uril‐controlled hydride migration under optimized conditions. The five recycled runs suggested the catalytic activity of the cucurbit[7]uril remained. The experimental analysis and DFT calculation disclosed the important role of supramolecular encapsulation of substrates within the cavity of the macrocyclic host to fix the phenyl groups on hydrobenzoin compounds and trigger the hydride migration, therefore, ketone was the prior product.

Production of renewable 1,3-pentadiene over LaPO4 via dehydration of 2,3-pentanediol derived from 2,3-pentanedione

1,3-Pentadiene plays an extremely important role in the production of polymers and fine chemicals. Herein, the LaPO4 catalyst exhibits excellent catalytic performance for the dehydration production of 1,3-pentadiene with 2,3-pentanediol, a C5 diol platform compound that can be easily obtained by hydrogenation of bio-based 2,3-pentanedione. The relationships of catalyst structure-acid/base properties-catalytic performance was established, and an acid-base synergy effect was disclosed for the on-purpose synthesis of 1,3-pentadiene. Thus, a balance between acid and base sites was required, and an optimized LaPO4 with acid/base ratio of 2.63 afforded a yield of 1,3-pentadiene as high as 61.5% at atmospheric pressure. Notably, the Brønsted acid sites with weak or medium in LaPO4 catalyst can inhibit the occurrence of pinacol rearrangement, resulting in higher 1,3-pentadiene production. In addition, the investigation on reaction pathways demonstrated that the E2 mechanism was dominant in this dehydration reaction, accompanied by the assistance of E1 and E1cb.

Rearrangements and Migrations along the Ferrocene Periphery: On the Way to Planar‐Chiral and (Multi)Substitution Patterns

AbstractThe functionalization of ferrocenes via intramolecular rearrangements is summarized. Focus will be directed on anionic, cationic and thermal/photo‐induced processes that enable the migration of functional groups along the periphery of the ferrocene's cyclopentadienyl rings. Anionic processes include halogen dance reactions and Fries rearrangements. The metalation procedures are discussed, which are essential for a regio‐ and stereoselective proceeding. Computational studies and electrochemical data are included to discuss stereoselective processes and reactivity differences. Positioning of a positive charge in close proximity to the ferrocenyl backbone induces Pinacol, Beckmann, and remote Fries rearrangements. Activation of an alkynyl functionality facilitates alkyne/vinylidene changes. Thermal rearrangements do not require an additional charge and are induced by N2 elimination, followed by nitrene/carbene formation via Curtius and Wolff rearrangements, respectively. The latter was exemplarily used for the ring contraction of [4]‐ into [3]ferrocenophanes.