Atom-economic Reaction Research Articles

Hydroaminoalkylation for the Catalytic Addition of Amines to Alkenes or Alkynes: Diverse Mechanisms Enable Diverse Substrate Scope

Hydroaminoalkylation is a powerful, atom-economic catalytic reaction for the reaction of amines with alkenes and alkynes. This C-H functionalization reaction allows for the atom-economic alkylation of amines using simple alkenes or alkynes as the alkylating agents. This transformation has significant potential for transformative approaches in the pharmaceutical, agrochemical, and fine chemical industries in the preparation of selectively substituted amines and N-heterocycles and shows promise in materials science for the synthesis of functional and responsive aminated materials. Different early transition-metal, late transition-metal, and photoredox catalysts mediate hydroaminoalkylation by distinct mechanistic pathways. These mechanistic insights have resulted in the development of new catalysts and reaction conditions to realize hydroaminoalkylation with a broad range of substrates: activated and unactivated, terminal and internal, C-C double and triple bonds with aryl or alkyl primary, secondary, or tertiary amines, including N-heterocyclic amines. By deploying select catalysts with specific substrate combinations, control over regioselectivity, diastereoselectivity, and enantioselectivity has been realized. Key barriers to widespread adoption of this reaction include air and moisture sensitivity for early transition-metal catalysts as well as a heavy dependence on amine protecting or directing groups for late transition-metal or photocatalytic routes. Advances in improved catalyst robustness, substrate scope, and regio-/stereoselective reactions with early- and late transition-metal catalysts, as well as photoredox catalysis, are highlighted, and opportunities for further catalyst and reaction development are included. This perspective shows that hydroaminoalkylation has the potential to be a disruptive and transformative strategy for the synthesis of selectively substituted amines and N-heterocycles from simple amines and alkenes.

New mechanistic insights into direct ethylene glycol synthesis from syngas over modified Rh carbonyl catalysts

Direct ethylene glycol (EG) synthesis from syngas as one of typical atom-economic reaction is a big challenge in catalysis, attracting wide attention in scientific research. Here, the mechanistic studies on direct syngas-to-EG conversion over the rhodium carbonyl catalyst Rh4(CO)12 modified by triethylamine (Et3N), 1,3-dimethyl-2-imidalidinone (DMI), and triisopropylphosphine (PiPr3) ligands were performed using combined density functional theory (DFT) calculation and the microkinetic modeling. The results demonstrate the significant improvement of selectivity from syngas to EG on going from Rh4(CO)12 to Rh4(CO)10(Et3N)(DMI) and Rh4(CO)10(DMI)(PiPr3) systems on account of the formation of CH2OH species being more favorable than CH3O. More importantly, the effect of different ligands makes a clear change in the carbon chain growth mechanism from the CO insertion into CH2OH in the Rh4(CO)10(DMI)(PiPr3) to the CHO coupling in the Rh4(CO)10(Et3N)(DMI). According to Bader charge and canonical molecular orbital analyses, it is suggested that the facilitated CHO coupling in the Rh4(CO)10(Et3N)(DMI) is associated with stronger electrostatic attraction and π-π conjugation between two CHO intermediates, and the π and σ bonding interactions between CHO and DMI. Such a fundamental mechanistic understanding reveals the nature of tuning the catalytic performance using different ligands, and also opens a new OHCCHO-mediated pathway for direct EG synthesis from syngas over Rh carbonyl catalysts.

Catalytic Hydrogenation of Epoxides to Alcohols.

Atom-economical catalytic reactions are a highly enticing strategy because all atoms of the starting materials are incorporated into the products. Catalytic hydrogenation of epoxides to alcohols is an attractive and alternative protocol to other synthetic methodologies for the synthesis of alcohols from alkenes. In the last two decades, catalytic hydrogenation of epoxides to alcohols has made remarkable progress in chemical synthesis. In this review, an overview of the catalytic hydrogenation of both terminal and internal epoxides to the corresponding alcohols is presented. An outline of both homogeneous and heterogeneous hydrogenation of epoxides to the corresponding alcohols is provided. Moreover, the selectivity, efficiency, and the reaction mechanisms of these epoxide hydrogenation reactions are highlighted.

Catalysis with Diboron(4)/Pyridine: Application to the Broad-Scope [3 + 2] Cycloaddition of Cyclopropanes and Alkenes.

In contrast to the extensive but non-recyclable use of tetraalkoxydiboron(4) compounds as stoichiometric reagents in diverse reactions, this article reports an atom-economical reaction using a commercial diboron(4) as the catalyst. The key to success was designing a catalytic cycle for radical [3 + 2] cycloaddition involving a pyridine cocatalyst to generate from the diboron(4) catalyst and reversibly mediate the transfer of boronyl radicals. In comparison with known [3 + 2] cycloaddition with transition metal-based catalysts, the current reaction features not only metal-free conditions, inexpensive and stable catalysts, and simple operation but also remarkably broadened substrate scope. In particular, previously unusable cyclopropyl ketones without an activating group and/or alkenes with 1,2-disubstitution and 1,1,2-trisubstitution patterns were successfully used for the first time. Consequently, challenging cyclopentane compounds with various levels of substitution (65 examples, 57 new products, up to six substituents at all five ring atoms) were readily prepared in generally high to excellent yield and diastereoselectivity. The reaction was also successfully applied in concise formal synthesis of an anti-obesity drug and building natural product-like complex bridged or spirocyclic compounds. Mechanistic experiments and computational investigation support the proposed radical relay catalysis featuring a pyridine-assisted boronyl radical catalyst. Overall, this work demonstrates the first approach to use tetraalkoxydiboron(4) compounds as catalysts and may lead to the development of new, green, and efficient transition metal-like boron-catalyzed organic reactions.

Diarylation of N- and O-nucleophiles through a metal-free cascade reaction

Diarylation of N- and O-nucleophiles through a metal-free cascade reaction

Structurally Diverse and Recyclable Isocyanate-Free Polyurethane Networks from CO2-Derived Cyclic Carbonates

Isocyanate-free chemistry and the introduction of dynamic bonds are a promising combination toward the development of more sustainable polyurethane (PU) networks. Here, we present the synthesis of reprocessable, isocyanate-free PU networks through atom-economical reactions for both monomers and polymers, valorizing CO2 as a building block. The monomers employed were five-membered cyclic carbonates prepared through an efficient (>99% conversion) reaction between CO2 and epoxides with high yield (up to 97% at a 100 gram scale), catalyzed by the moisture-tolerant and easily prepared DBU·I2 complex. The structural diversity of the monomers and the utilization of cystamine bearing the dynamic S–S motif realized PU networks with a finely tuned profile of thermal (Tg from −9 to 44 °C), mechanical (E from 0.2 to 1700 MPa), and viscoelastic properties (E′ from 0.03 to 5.5 MPa at 1 Hz). Facile recycling (100 °C, 20 min) of the networks was enabled thanks to the rapidly exchanging disulfide bonds and the modulated cross-link density. Moisture-induced plasticization of the networks was identified, and its effect on the properties of the networks was elucidated. The atom economy and energy-efficiency methodology, avoiding toxic reagents and preventing waste generation, make this approach an attractive and greener pathway to PU networks taking a step toward a circular plastic economy.

Green synthesis of various saturated S-heterocyclic scaffolds: an update

Abstract Development of reliable and eco-friendly novel schemes for the synthesis of organic compounds is an important step in the field of organic and medicinal chemistry. Green chemistry-based strategies involving use of catalysts, green solvents, atom economic reactions etc. play a key role because of their exceptional ability to minimize the toxicity or hazards of the side products and processes. With the use of these green techniques, a number of researchers were able to synthesis a wide range of heterocyclic compounds. This chapter highlights the potential and diverse biological activities of saturated sulphur containing heterocyclic compounds including thiirane, thiane, thiolane and many more. The aim of this chapter is to provide fresh perspective on the various techniques employed for the formation of C–S bond by summarizing all green synthesis from 2016 to 2021.

C-H bond activation and sequential addition to two different coupling partners: a versatile approach to molecular complexity.

Sequential multicomponent C-H bond addition is a powerful approach for the rapid, modular generation of molecular complexity in a single reaction. In this approach, C-H bonds are typically added across π-bonds or π-bond isosteres, followed by subsequent coupling to another type of functionality, thereby forming two σ-bonds in a single reaction sequence. Many sequential C-H bond addition reactions have been developed to date, including additions across both conjugated and isolated π-systems followed by coupling with reactants such as carbonyl compounds, cyanating reagents, aminating reagents, halogenating reagents, oxygenating reagents, and alkylating reagents. These atom-economical reactions transform ubiquitous C-H bonds under mild conditions to more complex structures with a high level of regiochemical and stereochemical control. Surprising connectivities and diverse mechanisms have been elucidated in the development of these reactions. Given the large number of possible combinations of coupling partners, there are enormous opportunities for the discovery of new sequential C-H bond addition reactions.

Experimental and theoretical investigation for the cycloaddition of carbon dioxide to epoxides catalyzed by potassium and boron co-doped carbon nitride

Much endeavor has been devoted to efficient heterogeneous catalysts for carbon dioxide (CO2) conversion to high-value chemicals. Meanwhile, the cycloaddition of CO2 to epoxides is considered as a green and atom-economy reaction to produce cyclic carbonates. Herein, a series of K, B co-doped CN with various doping contents (K, B-CN-X) were developed by simple one-step calcination of melamine and KBH4. B was confirmed to replace the C site and KN bond was formed, which was verified by XPS (X-ray photoelectron spectroscopy) and DFT (density functional theory) calculation. Particularly, K, B-CN-4 displayed the optimal catalytic performance in the presence of Bu4NBr (tetrabutylammonium bromide) cocatalyst for the CO2 cycloaddition with propylene oxide. Besides, K, B-CN-4/Bu4NBr catalyst exhibited good substrate versatility to various epoxides and excellent recycling performance. According to the DFT calculation on CO2 adsorption and experimental results, K, B-CN-4 presented satisfactory catalytic activity due to the enhanced CO2 adsorption after K and B dopings then the possible reaction mechanism was proposed. The promising K, B-CN-X catalyst presented an attractive application due to the simple, eco-friendly synthesis route for the efficient fixation of CO2.

A method to fabricate supported catalytic packing: Polydopamine as a "Double-Sided Adhesive" to prepare the fully covered seeding layer

BackgroundIn recent years, Supported catalytic packings (SCPs) with zeolite coating on metallic substrates have received extensive attention due to their satisfactory heat/mass transfer properties. MethodsHerein, high-performance SCP with HZSM-5 coating was fabricated by secondary growth method with polydopamine (PDA)-assisted seeding, where PDA was used as a "double-sided adhesive" sandwiched between supports and seeds. The atom-economic reaction of cyclohexene and acetic acid for cyclohexyl acetate production was carried out to evaluate the catalytic performance of as-fabricated SCPs. Significant FindingsDue to the strong adhesion of PDA, the uniform and high-coverage seeding layer was achieved under the optimized seeding conditions, then continuous HZSM-5 coating that possessed high crystallinity, rough surface, and intergranular voids was formed. Compared with SCP prepared by secondary growth method with the traditional dip coating seeding method, the catalytic activity and stable operation time of PDA-assisted SCP were increased by 50% and 57%, respectively. Furthermore, PDA-assisted seeding method is easy to conduct, indicating its great potential in practical applications.

Nickel(II)-Catalyzed [3 + 2] Cycloaddition of Nitrones and Allenoates to Access N-Vinylindoles and N-Vinylpyrroles.

A variety of N-vinylindoles and N-vinylpyrroles were prepared in moderate to good yields through the nickel(II)-catalyzed [3 + 2] cycloaddition of α,β-unsaturated nitrones with allenoates under mild reaction conditions. A rational mechanism for the formation of N-vinylindoles was proposed based on the 18O-labeled experiments and key intermediates detected by high-resolution mass spectrometry trace experiments. The present method highlights a nickel(II)-controlled cyclization, atom-economical reaction, broad substrate scope, good functional group tolerance, and high Z-stereoselectivity for the enamine bond.

Enantioselective Oxidative Multi-Functionalization of Terminal Alkynes with Nitrones and Alcohols for Expeditious Assembly of Chiral α-Alkoxy-β-amino-ketones.

Catalytic oxidative functionalization of alkynes has emerged as an effective method in synthetic chemistry in recent decades. However, enantioselective transformations via metal carbene intermediates are quite rare due to the lack of robust chiral catalysts, especially in the intermolecular versions. Herein, we report the first asymmetric three-component reaction of commercially available alkynes with nitrones and alcohols, which affords α-alkoxy-β-amino-ketones in good yields with high to excellent enantioselectivity using combined catalysis by an achiral gold complex and a chiral spiro phosphoric acid (CPA). Mechanistically, this atom-economic reaction involves a catalytic alkyne oxidation/ylide formation/Mannich-type addition sequence that uses nitrone as the oxidant and the leaving fragment imine as the electrophile, providing a novel method for multi-functionalization of commercially available terminal alkynes.

Four-Step Domino Reaction Enables Fully Controlled Non-Statistical Synthesis of Hexaarylbenzene with Six Different Aryl Groups*.

Hexaarylbenzene (HAB) derivatives are versatile aromatic systems playing a significant role as chromophores, liquid crystalline materials, molecular receptors, molecular‐scale devices, organic light‐emitting diodes and candidates for organic electronics. Statistical synthesis of simple symmetrical HABs is known via cyclotrimerization or Diels–Alder reactions. By contrast, the synthesis of more complex, asymmetrical systems, and without involvement of statistical steps, remains an unsolved problem. Here we present a generally applicable synthetic strategy to access asymmetrical HAB via an atom‐economical and high‐yielding metal‐free four‐step domino reaction using nitrostyrenes and α,α‐dicyanoolefins as easily available starting materials. Resulting domino product—functionalized triarylbenzene (TAB)—can be used as a key starting compound to furnish asymmetrically substituted hexaarylbenzenes in high overall yield and without involvement of statistical steps. This straightforward domino process represents a distinct approach to create diverse and still unexplored HAB scaffolds, containing six different aromatic rings around central benzene core.

Mild and Efficient Tunable Brønsted Acidic Ionic Liquid Catalyzed O-Acetylation and O-Trimethylsilylation with Trimethylsilyl Acetate (TMSOAc) and Hexamethyldisilazane (HMDS)

This report discloses a mild and efficient O-acetylation using easily accessible TMSOAc as a novel acetyl reagent and O-trimethylsilylation using HMDS for various alcohols catalyzed by tunable Brønsted acidic ionic liquids (TBAILs). Imidazolium-based TBAILs were prepared by a two-step atom-economic reaction and acidities measured by using UV-visible spectroscopy. Both protections for alcohols were accomplished at room temperature with good to excellent yields, while the products and TBAILs were separated by simple work-up for O-silylation and column chromatography for O-acetylation. Notably, with the simple post-process, TBAILs catalyst in this solvent free method easily recovered and recycled several times without significant degradation.

Recent Advances and the Prospect of Hypervalent Iodine Chemistry

AbstractNowadays, hypervalent iodine chemistry has remarkably advanced in parallel with the emergence of novel hypervalent iodine reagents. Hypervalent iodine reagents, due to their outstanding characteristics including rich reactivities, excellent chemoselectivity, stability, and environmental friendliness, are becoming more and more popular in the synthetic organic chemistry. In this Account, a number of recent elegant research works and our perspective on the future of hypervalent iodine chemistry is presented.1 Introduction2 Recent Advances and Discussion2.1 Novel Reactivities of Hypervalent Iodine Reagents2.2 Atom-Economical Reactions Promoted by Hypervalent Iodine Reagents2.3 Other Applications of Hypervalent Iodine Reagents2.4 The Applications of DFT Calculations in Elucidating Reaction Mechanism Involving Hypervalent Iodine Reagents3 Outlook and Conclusion

2,2′-(Arylmethylene)bis(3-hydroxy-5,5-dimethylcyclohex-2-enone) crystals formation via atom economy reaction and their antioxidant activity

2,2′-(Arylmethylene)bis(3-hydroxy-5,5-dimethylcyclohex-2-enone) crystals formation via atom economy reaction and their antioxidant activity

Exploiting Heavier Organochalcogen Compounds in Donor-Acceptor Cyclopropane Chemistry.

Donor-acceptor (D-A) cyclopropanes have gained increased momentum over the past two decades. The use of these highly strained three-membered entities paved the way to innovative and original transformations yielding complex cyclic and acyclic architectures that otherwise might be difficult to address. Since the fundamentals were laid by Wenkert and Reissig in the late 1970s, the field has flourished impressively including asymmetric transformations as well as elegant synthetic applications in the construction of natural occurring products. In this Account, we aim to highlight especially our efforts in the context of an efficient access to sulfur- and selenium-containing compounds, of either cyclic or open-chain nature, by exploiting D-A cyclopropane chemistry. Light will be shed on the three fundamental transformations: ring-opening reactions, cycloadditions, and rearrangements.Our synthetic endeavors started back in 2011 guided by quantum chemical studies to obtain 3,3'-linked bisthiophenes along with an unprecedented rearrangement delivering sulfur- and selenium-containing cagelike scaffolds. Inspired by these surprising results, we further deepened our efforts to the construction of new sulfur-carbon and selenium-carbon bonds within the context of D-A cyclopropane chemistry. In the first instance, we capitalized on the great versatility of organosulfur and organoselenium compounds regarding their amphiphilic character to act either as nucleophilic or as electrophilic species. By such an approach, ring-openings via a nucleophilic attack of sulfenyl and selenyl halides furnished 1,3-bishalochalcogenated products. A similar protocol led us to a desymmetrization reaction of meso-cyclopropyl carbaldehydes employing novel chiral imidazolidinone organocatalysts. In contrast, electrophilic sulfur was supplied by N-(arylthio)succinimide substrates to access thiolated γ-amino acid derivatives and their selenium equivalents.Combining the highly reactive thiocarbonyl compounds and vicinal donor-acceptor substituted cyclopropanes opened new vistas in the field of atom-economic cycloaddition reactions to build up sulfur-containing heterocycles of various sizes. The first systematic study of such transformations was made by our group in 2017 leading to highly decorated thiolanes, whereas an intramolecular approach furnished thia-[n.2.1]bicyclic ring systems. Our investigations were then successfully extended to the synthesis of tetrahydroselenophenes by using capricious selenoketones. Recently, we were able to yield the unsaturated analogues, selenophenes, by a (3 + 2)-cycloaddition of D-A cyclopropanes with ammonium selenocyanates followed by oxidation. The formal insertion of thioketenes was realized by employing 3-thioxocyclobutanones as surrogates for disubstituted thioketenes to obtain 2-substituted tetrahydrothiophenes bearing a semicyclic double bond via a (3 + 2) spiroannulation/(2 + 2) cycloreversion sequence. Even the formation of seven-membered S-heterocycles was realized by (4 + 3)-cycloaddition processes. In 2016, we demonstrated the synthesis of benzo-fused dithiepines from in situ generated ortho-bisthioquinones, whereas the utilization of thia-Michael systems as a hetero-4π-component delivered tetrahydrothiepine derivatives containing just one sulfur atom embedded in the ring system.

High yield room temperature conversion of carbon dioxide into cyclic carbonates catalyzed by mixed metal oxide (CuO‐ZnO) nano‐flakes/micro‐flakes (Cozi‐nmf)

Capturing and converting carbon dioxide (CO2) into useful organic molecules and polymers is the best way of alleviating excessive release of it from industrial sources to the environment. Cyclic carbonate synthesis by cycloaddition from CO2 and epoxides through a catalytic process is a 100% atom economic reaction established five decades ago. Despite the availability of many efficient catalytic systems, there are shortcomings in either tedious preparatory procedure of catalyst, separation problem associated with homogeneous catalysis, or the requirement of pure CO2. In this work, we report the catalytic system based on copper and zinc mixed metal oxides (CuO‐ZnO) nano‐flakes/micro‐flakes (Cozi‐nmf) for cycloaddition of CO2 with various epoxides at room temperature under solvent‐free conditions. The novel recyclable heterogeneous catalyst was prepared via a simple procedure successfully at room temperature by grinding process. The synthesis of both catalyst and cyclic carbonates described here is greener and used inexpensive source materials to produce them. The yields of the synthesized cyclic carbonates were more than 95%, except for many reactions. The high efficiency of Cozi‐nmf as a catalyst is explained based on the availability of the bare catalyst surface, which promoted the hindrance free movement of electrons and adsorption of substrate effectively.

Photo-Mediated Intermolecular Coupling of Alkenes with Ketones via Acyloxy Nitroso Compounds.

An atom-economic intermolecular radical addition reaction of acyloxy nitroso compounds to electron-deficient alkenes mediated by visible light is reported. The starting nitroso derivatives are readily prepared by oxidation of the corresponding oximes prepared from ketones and the overall transformation represents an oxidative coupling of a ketone with a Michael acceptor. The cascade proceeds smoothly under mild conditions, providing a series of valuable functionalized oximes in moderate to good yields. Mechanistic studies suggest that these cascades proceed via addition/coupling processes that are controlled by the persistent radical effect (PRE) with NO acting as the persistent species.

Investigations into a Stoichiometrically Equivalent Intermolecular Oxidopyrylium [5 + 2] Cycloaddition Reaction Leveraging 3-Hydroxy-4-pyrone-Based Oxidopyrylium Dimers.

Oxidopyrylium [5 + 2] cycloaddition reactions are powerful strategies for constructing complex bicyclic architectures. However, intermolecular cycloadditions of oxidopyrylium ylides are limited due to competing dimerization processes; consequently, high equivalents of dipolarophiles are often used to help intercept the ylide prior to dimerization. Recent studies by our lab have revealed that oxidopyrylium dimers derived from 3-hydroxy-4-pyrones are capable of reverting back to ylides in situ and as a result can be used as clean oxidopyrylium ylide sources. The following manuscript investigates intermolecular cycloaddition reactions between 3-hydroxy-4-pyrone-derived oxidopyrylium dimers and stoichiometrically equivalent ratios of alkyne dipolarophiles under thermal conditions. With certain reactive alkynes, pure cycloadducts can be obtained following a simple evaporation of the solvent, which is a benefit of the completely atom-economical reaction conditions. However, when less reactive alkynes are used the yields suffer due to a competing dimer rearrangement. Finally, when reactive-yet-volatile alkynes are used, such as methyl propiolate, competing 2:1 ylide/alkyne cycloadducts are observed. Intriguingly, these complex cycloadducts, which can be obtained in good yields from the pure cycloadducts, form with high regio- and stereoselectivities; however, both the regio-and stereoselectivities differ remarkably based on the source of the oxidopyrylium ylide.