Gold‐Catalyzed Formal C−C Bond Insertion Reaction of 2‐Aryl‐2‐diazoesters with 1,3‐Diketones

The transition‐metal‐catalyzed formal C−C bond insertion reaction of diazo compounds with monocarbonyl compounds is well established, but the related reaction of 1,3‐diketones instead gives C−H bond insertion products. Herein, we report a protocol for a gold‐catalyzed formal C−C bond insertion reaction of 2‐aryl‐2‐diazoesters with 1,3‐diketones, which provides efficient access to polycarbonyl compounds with an all‐carbon quaternary center. The aryl ester moiety plays a crucial role in the unusual chemoselectivity, and the addition of a Brønsted acid to the reaction mixture improves the yield of the C−C bond insertion product. A reaction mechanism involving cyclopropanation of a gold carbenoid with an enolate and ring‐opening of the resulting donor–acceptor‐type cyclopropane intermediate is proposed. This mechanism differs from that of the traditional Lewis‐acid‐catalyzed C−C bond insertion reaction of diazo compounds with monocarbonyl compounds, which involves a rearrangement of a zwitterion intermediate as a key step.     

Phosphine‐Catalyzed Enantioselective γ‐Addition of 3‐Substituted Oxindoles to 2,3‐Butadienoates and 2‐Butynoates: Use of Prochiral Nucleophiles

The first phosphine‐catalyzed enantioselective γ‐addition with prochiral nucleophiles and 2,3‐butadienoates as the reaction partners has been developed. Both 3‐alkyl‐ and 3‐aryl‐substituted oxindoles could be employed in this process, which is catalyzed by a chiral phosphine that is derived from an amino acid, thus affording oxindoles that bear an all‐carbon quaternary center at the 3‐position in high yields and excellent enantioselectivity. The synthetic value of these γ‐addition products was demonstrated by the formal total synthesis of two natural products and by the preparation of biologically relevant molecules and structural scaffolds.     

Carbazoles from the [4C+2C] Reaction of 2,3‐Allenols with Indoles

A mild and efficient method using readily available 1‐aryl‐2,3‐allenols and unprotected‐N indoles, Au⁺‐catalyzed cyclization, and aromatization to afford the final [4C+2C] products, carbazoles 4, with an excellent selectivity, is reported. The reaction demonstrates excellent regioselectivity and allows the N?H unit to undergo reactivity unprotected. A mechanism involving a spiropolycyclic intermediate has been proposed and synthetic application is also demonstrated.     

Total Syntheses of (+)‐Polygalolide A and (+)‐Polygalolide B: Elucidation of the Absolute Stereochemistry and Biogenetic Implications

The total syntheses of (+)‐polygalolide A and (+)‐polygalolide B have been completed by using a carbonyl ylide cycloaddition strategy. Three of the four stereocenters, including two consecutive tetrasubstituted carbon atoms at C2 and C8, were incorporated through internal asymmetric induction from the stereocenter at C7 by a [Rh₂(OAc)₄]‐catalyzed carbonyl ylide formation/intramolecular 1,3‐dipolar cycloaddition sequence. The arylmethylidene moiety of these natural products was successfully installed by a Mukaiyama aldol‐type reaction of a silyl enol ether with a dimethyl acetal, followed by elimination under basic conditions. We have also developed an alternative approach to the carbonyl ylide precursor based on a hetero‐Michael reaction. This approach requires 18 steps, and the natural products were obtained in 9.8 and 9.3 % overall yields. Comparison of specific rotations of the synthetic materials and natural products suggests that polygalolides are biosynthesized in nearly racemic forms through a [5+2] cycloaddition between a fructose‐derived oxypyrylium zwitterion with an isoprene derivative.     

Chemical reaction kinetics measurements for single and blended amines for CO2 postcombustion capture applications

The present study has established the direct pseudo–first‐order reaction kinetics of different aqueous‐based single and blended amines over the temperature range of 298.15‐313.15 K using stopped‐flow techniques. The single amines include one primary amine (monoethanolamine, MEA), two secondary amines (diethanolamine, DEA and 2‐ethyl(amino)ethanol, 2EAE), four tertiary amines (N‐methyldiethanolamine, MDEA, 1‐dimethylamino‐2‐propanol, 1DMA2P, 3‐dimethylamino‐1‐propanol, 3DMA1P, and 2‐dimethylaminoethanol, 2DMAE), one sterically hindered amine (2‐amino‐2‐methyl‐1‐propanol, AMP), and one cyclic diamine (piperazine, PZ). The blend systems used are MEA/PZ, DEA/PZ, MDEA/PZ, AMP/PZ, MEA/AMP, MDEA/2EAE, 1DMA2P/2EAE, 3DMA1P/2EAE, and 2DMAE/2EAE. Different reaction mechanisms for the reaction of CO₂ with aqueous solutions of amines, such as base‐catalysis, zwitterion, termolecular, hybrid of zwitterion, hybrid of base‐catalysis‐zwitterion, and hybrid of base‐catalysis‐termolecular reaction mechanisms, are used to correlate the experimental data. For the single amines, the zwitterion mechanism is well suited to fit the experimental data of primary, secondary, sterically hindered and cyclic amines with an absolute average deviation (AAD%) less than 5%. The base‐catalysis mechanism fits the experimental data of all the tertiary amines well with an AAD less than 5%. For the blends, the hybrid of zwitterion mechanism fits the experimental data of MEA/PZ, DEA/PZ, AMP/PZ, and MEA/AMP well with an AAD less than 5%, whereas the hybrid of base‐catalysis‐zwitterion mechanism fits the experimental data of MDEA/PZ, MDEA/2EAE, 1DMA2P/2EAE, 3DMA1P/2EAE, and 2DMAE/2EAE well with an AAD less than 5%.     

Asymmetric Dual‐Reagent Catalysis: Mannich‐type Reactions Catalyzed by Ion Pair

The combination of a new bifunctional phosphine and an acrylate generate a zwitterion in situ and it serves as an efficient catalyst for asymmetric reactions through a homogeneous ion‐pairing mode. This new catalytic system has been successfully applied to Mannich‐type reactions to give excellent results and it demonstrates a broad substrate scope. Such reactivity is not accessible with general organophosphine catalytic modes. Preliminary investigations into the mechanism are also presented.     

Synthesis and decrosslinking of networked polymers having zwitterion structure consisted by cyclic amidine and isothiocyanate

We have already found that the polymers, which are obtained by the polymerization of 4‐vinylphenyl isothoiocyanate after the zwitterion formation with cyclic amidines, are networked through the ionic interaction among the zwitterions becoming insoluble to various solvents. We report here on the results of the reaction of nucleophilic reagents such as amines and alcohols with the zwitterionic adduct to investigate about the decrosslinking through the resolution of ionic interactions. In the model reactions of amines and alcohols with the zwitterion compounds, which were consisted of the phenyl isothiocyanate and cyclic amidines, the reaction of nucleophilic reagents and zwitterionic adducts having methyl group at the 2‐position of the amidine proceed quantitatively. Based on the model reaction, such nucleophilic addition was applicable to decrosslinking reaction of the networked polymers containing the zwitterion structure in the side‐chain. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2131–2137     

Kinetics of the reaction of carbon dioxide with blends of amines in aqueous media using the stopped‐flow technique

The effect of mixing 2‐amino‐2‐methyl‐1‐propanol (AMP) with a primary amine, monoethanolamine (MEA), and a secondary amine, diethanolamine (DEA), on the kinetics of the reaction with carbon dioxide in aqueous media has been studied at 298, 303, 308, and 313 K over a range of blend composition and concentration. The direct stopped‐flow conductimetric method has been used to measure the kinetics of these reactions. The proposed model representing the reaction of CO₂ with either of the blends studied is found to be satisfactory in determining the kinetics of the involved reactions. This model is based on the zwitterion mechanism for all the amines involved (AMP, MEA, and DEA). Blending AMP with either of the amines results in observed pseudo‐first‐order reaction rate constant values (k_o) that are greater than the sum of the k_o values of the respective pure amines. This is due to the role played by one amine in the deprotonation of the zwitterion of the other amine. Steric factor and basicity of the formed zwitterion and the deprotonating species have a great bearing in determining the rate of the reactions studied. © 2005 Wiley Periodicals, Inc. Int J Chem Kinet 37: 391–405, 2005     

Palladium(II)‐Catalyzed Oxidative Cyclization of Allylic Tosylcarbamates: Scope,Derivatization, and Mechanistic Aspects

A highly selective oxidative palladium(II)‐catalyzed (Wacker‐type) cyclization of readily available allylic tosylcarbamates is reported. This operationally simple catalytic reaction furnishes tosyl‐protected vinyl‐oxazolidinones, common precursors to syn‐1,2‐amino alcohols, in high yield and excellent diasteroselectivity (>20:1). It is demonstrated that both stoichiometric amounts of benzoquinone (BQ) as well as aerobic reoxidation (molecular oxygen) is suitable for this transformation. The title reaction is shown to proceed through overall trans‐amidopalladation of the olefin followed by β‐hydride elimination. This process is scalable and the products are suitable for a range of subsequent transformations such as: kinetic resolution (KR) and oxidative Heck‐, Wacker‐, and metathesis reactions.     

Migratory Arylboration of Unactivated Alkenes Enabled by Nickel Catalysis

An unprecedented arylboration of unactivated terminal alkenes, featuring 1,n‐regioselectivity, has been achieved by nickel catalysis. The nitrogen‐based ligand plays an essential role in the success of this three‐component reaction. This transformation displays good regioselectivity and excellent functional‐group tolerance. In addition, the incorporation of a boron group into the products provides substantial opportunities for further transformations. Also demonstrated is that the products can be readily transformed into pharmaceutically relevant molecules. Unexpectedly, preliminary mechanistic studies indicate that although the metal migration favors the α‐position of boron, selective and decisive bond formation is favored at the benzylic position.     

An Unexpected Result of the Reaction of Benzothioamide Derivatives with 2‐Aryl‐2‐bromoacetonitriles

Unexpectedly, in the reaction of 2‐bromo‐2‐phenylacetonitrile derivatives with 2 mol‐equiv. of benzothioamide in DMSO, 3,5‐diaryl‐1,2,4‐thiadiazoles were obtained in excellent yields (83–90%) and in short reaction times (5–10 min). It is found that, in DMF, a quite different reaction takes place and 2,5‐diaryl‐1,3‐thiazol‐4‐amines are formed as the main products.     

Cycloadditions of Bifunctional Vinyl Ethers with Electrophilic Alkenes through Tetramethylene Zwitterion Intermediates

Bifunctional vinyl ethers react with electron‐poor alkenes to cyclobutanes in good yields. The second C?C bond reacted with neither the cyclobutane nor its zwitterion intermediate, even on heating. Cyclobutanes formed from ‘tetracyanoethylene’ ( 8 ) were transformed into tetrahydropyridines by reaction of the corresponding zwitterion with MeCN as the solvent. In contrast, cyclobutanes formed from dimethyl (dicyanomethylidene)propanedioate ( 9 ) did not react with MeCN, which is ascribed to diminished stabilization of the zwitterion intermediate, and increased steric effects. These results extend the classical studies of Huisgen and his co‐workers.     

Reactions of carbanions with 2,4‐dinitrofluorobenzene leading to stable heptatrienide moieties

Reactions of NCCH₂COOMe 1a and CH₂(CN)₂ 1b with 2,4‐dinitrofluorobenzene 2 at the presence of Et₃ N result in deeply colored crystalline stable salts 4a,4b with anions that contain a system of conjugated bonds. Similar reaction of 2 with phosphorus‐containing zwitterion 6 bearing ethoxy‐ and cyano‐groups at the carbanion center is the first example of the reaction leading to the formation of P‐zwitterion 9 with a negatively charged heptatriene moiety. This reaction proceeds via a new route of decomposition of the intermediate σ‐complex 7 occurring with formation of ethylfluoroformate. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:108–115, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20267     

Enantioselective Synthesis of Tropanes: Brønsted Acid Catalyzed Pseudotransannular Desymmetrization

The enantioselective synthesis of tropanols has been accomplished through chiral phosphoric acid catalyzed pseudotransannular ring opening of 1‐aminocyclohept‐4‐ene‐derived epoxides. The reaction proceeds together with the desymmetrization of the starting material and leads to the direct formation of the 8‐azabicyclo[3.2.1]octane scaffold with excellent stereoselectivity. The synthetic applicability of the reaction was demonstrated by the enantioselective synthesis of the two natural products (?)‐α‐tropanol and (+)‐ferruginine.     

CO2 incorporation reaction using arynes: straightforward access to benzoxazinone

A zwitterion, generated from an aryne and an imine, has been demonstrated to serve as an excellent molecular scaffold for capturing CO2, which results in the straightforward formation of diverse benzoxazinones.     

Multicomponent Double Diels–Alder/Nazarov Tandem Cyclization of Symmetric Cross‐Conjugated Diynones to Generate [6‐5‐6] Tricyclic Products

The construction of complex polycyclic terpenoid products in an efficient and step‐economical manner using multicomponent and tandem processes is highly valuable. Herein, we report a tandem cyclization sequence that initiates with a multicomponent double Diels–Alder reaction of cross‐conjugated diynones, followed by a Nazarov cyclization to efficiently produce [6‐5‐6] tricyclic products with excellent regio‐ and diastereoselectivity. This methodology generates five new carbon–carbon bonds, three rings, quaternary or vicinal quaternary carbons, and stereogenic centers in a one‐pot reaction.     

Zwitterionic Salts from the Reaction of Symmetrical and Unsymmetrical (thio)Barbituric Acids with 2‐Pyridinecarbaldehyde under Solvent‐free Condition

A simple and efficient synthesis for the preparation of unusual charge‐separated pyridinium (thio)barbiturate zwitterion derivatives was achieved via a one‐pot reaction of (thio)barbituric acid derivatives and 2‐pyridinecarbaldehyde under solvent‐free condition and also in methanol under refluxing. The structure of the compounds was confirmed by ¹H NMR, ¹³C NMR, FT‐IR, mass and X‐ray analysis. The mechanism of the formation is discussed. Instead, no related pyridinium zwitterion was afforded from the reaction between dimedone and 2‐pyridinecarbaldehyde under the same conditions and its xanthene derivative was obtained.     

Palladium‐Catalyzed Carbonylative Coupling of (2‐Azaaryl)methyl Anion Equivalents with (Hetero)Aryl Bromides

Conditions for the palladium‐catalyzed coupling of (2‐pyridyl)acetones with aryl bromides have been developed. Followed by an acid‐promoted deacetylation step, the desired 1‐(het)aryl‐2‐(2‐pyridyl)ethanones were obtained in good to excellent yields with high functional group tolerance. Test reactions revealed that both the addition of MgCl₂ and a specifically positioned heteroatom in the heteroaromatic ring were crucial for product formation indicating the importance of a chelated intermediate in the reaction mechanism. The reaction conditions proved suitable for a number of 5‐ and 6‐membered heteroaromatic starting materials affording all products in good yields. The utility of the obtained 1‐(het)aryl‐2‐(2‐pyridyl)ethanones was demonstrated by the straightforward synthesis of several multiaromatic derivatives in only few additional steps.     

A Biomimetic Heteroditopic Receptor for Zwitterions in Protic Media

The efficient synthesis of calix[6]cryptothiourea 6 was achieved through a two‐step sequence that involves a key [1+1] macrocyclization step. It was shown by NMR spectroscopy that this heteroditopic receptor can bind zwitterions in protic media with an outstanding selectivity for β‐alanine betaine G5 , which is likely due to a high complementarity between the two partners. This result constitutes a rare example of cavity complexation of a zwitterion by a calix[6]arene. In comparison with the parent urea‐based receptors, 6 behaves as a much more efficient host for betaines. This strengthening of the binding properties is due to the better preorganization of the tripodal hydrogen‐bonding cap as well as to the higher acidity of the thiourea groups and their poor ability to self‐associate. Remarkably, host 6 is able to perform solid–liquid as well as liquid–liquid extraction of G5 . Finally, 6 provides an excellent structural model for the binding site of glycine betaine G4 encountered in natural systems.