Hydrogen-bonding Catalysis Research Articles

Impact of a homogeneous hydrogen bond catalysis for the ethyl (hetero)arylidene cyanoacetate preparation in the presence of TMDP

Impact of a homogeneous hydrogen bond catalysis for the ethyl (hetero)arylidene cyanoacetate preparation in the presence of TMDP

Asymmetric Photoinduced Excited-State Nazarov Reaction.

We report herein the first asymmetric photoinduced excited-state Nazarov reaction of non-aromatic dicyclic divinyl ketones by using hydrogen-bonding catalysis. The enantioselectivity of photoinduced electrocyclization is highly dependent on the structural features of the substrate and its interaction with chiral catalysts. For the simple dicyclic divinyl ketone substrates, there is no discernible selectivity of the hydrogen bond coordination between the thiourea and carbonyl groups of the substrates in the ground state. However, we found that the direction of the electrocyclization was well controlled in each coordination model and the N,N'-dimethylamine motif acts as a base in the regioselective deprotonation process, which leads to the formation of two stereoisomers with high enantioselectivity. Photolysis of dicyclic divinyl ketones bearing a 1,3-dioxolane motif in the presence of bifunctional hybrid peptide-thiourea chiral catalysts gave the tricyclic cis-hydrofluorenones with good enantioselectivity. Mechanistic and DFT studies suggested that the amide and thiourea groups in the bifunctional chiral catalysts play a key role as H-bond donors, which coordinate with both the carbonyl group and the 1,3-dioxolane motif to provide a more favorable chiral species, and control the direction of the electrocyclization. Due to the presence of the rigid 1,3-dioxolane ring, the deprotonation/protonation process occurs regiospecifically with high driving force. This photo-electrocyclization is mild (room temperature and neutral solution), which results a broad reaction scope and functional group tolerance and demonstrates its synthetic potential in organic synthesis.

Asymmetric organocatalytic synthesis of chiral homoallylic amines.

In recent decades, the chiral allylation of imines emerged as a key methodology in the synthesis of alkaloids and natural products with 4-, 5- and 6-membered cyclic amine motifs. Initially reliant on stoichiometric reagents, synthetic chemists predominantly used N-substituted chiral imines, organometallic chiral reagents and achiral reagents with an equimolar chiral controller. However, recent years have witnessed the rise of asymmetric transition-metal catalysts and, importantly, organocatalytic allylation, reshaping the landscape of modern synthetic chemistry. This review explores the latest developments in the asymmetric allylation of imines, encompassing cutting-edge advances in hydrogen-bond catalysis and non-classical approaches. Furthermore, practical examples showcasing the application of these innovative methodologies in total synthesis are presented.

Catalytic Asymmetric Redox-Neutral [3+2] Photocycloadditions of Cyclopropyl Ketones with Vinylazaarenes Enabled by Consecutive Photoinduced Electron Transfer.

Consecutive photoinduced electron transfer (ConPET) is a powerful and atom-economical protocol to overcome the limitations of the intrinsic redox potential of visible light-absorbing photosensitizers, thereby considerably improving the substrate and reaction types. Likely because such an exothermic single-electron transfer (SET) process usually does not require the aid of chiral catalysts, resulting in an inevitable racemic background reaction, notably, no enantioselective manifolds have been reported. Herein, we report on the viability of cooperative ConPET and chiral hydrogen-bonding catalysis for the [3+2] photocycloaddition of cyclopropyl ketones with vinylazaarenes. In addition to enabling the first use of olefins that preferentially interact with chiral catalysts, this catalysis platform paves the way for the efficient synthesis of pharmaceutically and synthetically important cyclopentyl ketones functionalized by azaarenes with high yields, ees and dr. The robust capacity of the method can be further highlighted by the low loading of the chiral catalyst (1.0 mol %), the good compatibility of both 2-azaarene and 3-pyridine-based olefins, and the successful concurrent construction of three stereocenters on cyclopentane rings involving an elusive but important all-carbon quaternary.

Halogen Bond Catalysis: A Physical Chemistry Perspective.

As important noncovalent interactions, halogen bonds have been widely used in material science, supramolecular chemistry, medicinal chemistry, organocatalysis, and other fields. In the past 15 years, halogen bond catalysis has become a developed field in organocatalysis for the catalysts' advantages of being environmentally friendly, inexpensive, and recyclable. Halogen bonds can induce various organic reactions, and halogen bond catalysis has become a powerful alternative to the fully explored hydrogen bond catalysis. From a physical chemistry view, this perspective provides an overview of the latest progress and key examples of halogen bond catalysis via activation of the lone pair systems of organic functional group, π systems, and metal complexes. The research progresses in halogen bond catalysis by our group were also introduced.

Cooperative Triple Catalysis Enables Deaminative α-Indolmethylation of Carbonyl Compounds with Gramines.

α-Functionalization of carbonyl compounds is an important reaction in synthetic chemistry. However, the development of novel synthetic strategies to realize this reaction is challenging. This study describes the α-indolmethylation of carbonyl compounds using cooperative copper, amine, and hydrogen-bond catalysis. This reaction provides a novel and efficient strategy for developing indolmethylated carbonyl compounds by deaminative coupling of gramines.

Selectively self-recyclable, highly transparent and fire-safe polycarbonate plastic enabled by thermally responsive phosphonium-phosphate.

Both the circular economy and fire-safety of polymer plastics have become a global consensus. Herein, an integrated strategy for selectively self-recyclable, highly-transparent and fire-safe polycarbonate plastic is proposed by thermally responsive phosphonium-phosphate (DP). During its service life, DP, as a flame-retardant with good compatibility, enables polycarbonate plastic with high transparency in visible light, excellent self-extinguishing and high fire-safety. After consumption, DP, as a catalyst, triggers the selective self-recycling of DP-containing polycarbonate in mixed plastics and even in same-kind polycarbonate plastics without an external catalyst. Importantly, the oxygen-consuming mechanism at high temperature in fire accidents (>350 °C) and the double hydrogen bond catalysis mechanism at a lower temperature (180 °C) of DP are key to the life cycle management of polycarbonate from use-stage to post-consumption. This work inspires a new solution to plastic pollution by designing sustainable plastics that satisfy both service-stage and end-of-life criteria, striving towards a zero-waste circular economy.

Asymmetric synthesis of (R)-baclofen and (3S,4S)-tetflupyrolimet via "on water" organocatalytic addition reactions: a tip on catalyst screening.

This work demonstrates asymmetric synthesis of the GABA derivative (R)-baclofen and a new herbicidal mode-of-action inhibitor (3S,4S)-tetflupyrolimet featuring low loading (0.5 mol%) organocatalytic addition reactions of dithiomalonates to nitrostyrenes under "on water" conditions. Importantly, we observed that increasing the hydrophobicity of the catalyst does not guarantee improved catalytic performance under "on water" conditions and the trends in the catalytic efficiency of different HBD catalysts under "on water" conditions (with hydrophobic additives) align more closely with those observed in pure hydrophobic organic solvents. These findings propose a valuable tip for screening organocatalysts in developing asymmetric hydrogen-bonding catalysis under "on water" conditions.

Hydrogen-bonding catalysis of the degradation of polyethylene glycol to 1,4-dioxane over OH-functionalized ionic liquid.

Novel hydrogen-bonding-catalyzed upcycling of polyethylene glycol (PEG) waste to 1,4-dioxane over OH-functionalized ionic liquids (ILs) under mild (≥80 °C), solvent- and metal-free conditions was developed through a theoretical computation-assisted design. Notably, 1,4-dioxane was spontaneously separated due to its immiscibility with ILs.

Recent Asymmetric Phase-Transfer Catalysis with Chiral Binaphthyl-Modified and Related Phase-Transfer Catalysts over the Last 10 Years.

In this personal account, we describe our recent advances in the three types of phase-transfer catalysis for various transformations including asymmetric induction: Firstly, asymmetric phase-transfer catalysis with Maruoka-type C2 -symmetric chiral biaryl-modified tetraalkylammonium salts and phosphonium salts; Secondly, asymmetric phase-transfer catalysis under base-free and neutral conditions; Thirdly, hydrogen-bonding catalysis using tetraalkylammonium and trialkylsulfonium salts. These three different strategies are illustrated by using various phase-transfer catalyzed transformations.

Cation–anion confined hydrogen-bonding catalysis strategy for ring-closing C–O/O–H metathesis of alkoxy alcohols under metal-free conditions

Cation–anion confined hydrogen-bonding-catalyzed ring-closing C–O/O–H metathesis of alkoxy alcohols to O-heterocycles is realized over OH-functionalized ionic liquids under metal-free and mild conditions (≥70 °C).

Enantioselective Michael Addition/Cyclization/Desymmetrization Sequence of Prochiral Cyclic Hemiacetals and Nitroolefins: Synthesis of Chiral Oxygen-Bridged Bicyclic Compounds.

The organocatalytic enantioselective Michael addition of functionalized prochiral cyclic hemiacetals and nitroolefins has been developed under cooperative enamine and hydrogen bond catalysis. The obtained chiral hemiacetal intermediates could be used in the subsequent diastereocontrolled cyclization/desymmetrization divergent process to access (1) 9-oxabicyclo[3.3.1]nonane or 8-oxabicyclo[3.2.1]octane frameworks via oxocarbenium ion-mediated Friedel-Crafts cyclization, and (2) 2,9-dioxabicyclo[3.3.1]nonane frameworks via intramolecular nucleophilic cyclization. Experimental results suggest that there is neighboring group participation controlling the diastereoselectivities of the desymmetrization process.

Cooperative Photoredox and Chiral Hydrogen-Bonding Catalysis Enables Enantioselective Radical Coupling

Cooperative Photoredox and Chiral Hydrogen-Bonding Catalysis Enables Enantioselective Radical Coupling

Conjugate addition-enantioselective protonation to forge tertiary stereocentres α to azaarenes via cooperative hydrogen atom transfer and chiral hydrogen-bonding catalysis

Cooperative hydrogen atom transfer and chiral hydrogen-bonding catalysis as a new platform for the asymmetric synthesis of azaarene derivatives is reported. By using a tetrabutylammonium decatungstate as the photocatalyst and a chiral phosphoric acid as the hydrogen-bonding catalyst, transformations of a variety of commercially available hydrocarbons and silanes with diverse α-branched 2-vinylazaarenes could efficiently experience a tandem radical conjugate addition and enantioselective protonation process, providing a convenient and fully atom economical approach to access a range of valuable enantioenriched α-tertiary azaarenes in high yields with good to excellent enantioselectivities (up to 93% ee). Through the direct use of tert-butyl methylcarbamate as the feedstock, this method enables a highly practical and concise synthesis of the enantiomerically pure medicinal molecule pheniramine (Avil).

Organo-Polyoxometalate-Based Hydrogen-Bond Catalysis.

Several urea-inserted organo-polyoxometalates (POMs) derived from polyoxotungstovanadate [P2 V3 W15 O61 ]9- were prepared. The insertion of the carbonyl into the polyoxometallic framework activates the urea toward Hydrogen-bond catalysis. This was shown on the Friedel-Crafts arylation of trans-β-nitrostyrene. Modelling shows that the most stable form of the organo-POMs features a cis-trans arrangement of the two N-H bonds, but that the likely catalytically active trans-trans form is accessible at room temperature. Finally, it is possible that the oxo substituents next to the vanadium atoms may help the approach of the nucleophile via H-bonding.

Ionic-Liquid-Catalyzed Approaches under Metal-Free Conditions.

ConspectusMetal-free catalysis is a promising protocol to access chemicals without metal contamination. Ionic liquids (ILs) that are entirely composed of organic cations and inorganic/organic anions have emerged as promising alternatives to molecular solvents and metal catalysts due to their unique properties such as structural tunability, the coexistence of multiple interactions among ions (e.g., electrostatic interaction, hydrogen bonding, van de Waals forces, acid/base interactions, hydrophilic/hydrophobic interactions, etc.), unique affinity for a wide range of chemicals, good chemical and thermal stability, and quite low volatility. ILs have shown potential applications in various chemical processes.In this Account, we systematically described our most recent work on IL-catalyzed approaches under metal-free conditions. The first section presents the IL-catalyzed strategies toward the transformation of CO2 to value-added chemicals, focusing on the CO2-reactive IL-catalyzed CO2 transformation to various heterocycles and the IL-catalyzed reductive transformation of CO2 to chemicals. In these approaches, we designed task-specific ILs that are able to chemically capture and activate CO2 via forming anion-based carbonate/carbamate or cation-based carboxylate/carbamate intermediates, thus further accomplishing its transformation to a series of heterocycles including quinazoline-2,4(1H,3H)-diones, cyclic carbonates, 2-oxazolidinones, oxazolones, and benzimidazolones under metal-free conditions. For the IL-catalyzed approaches to reducing CO2 with hydrosilanes to chemicals, we employed ILs capable of activating the Si-H bond in hydrosilanes and the N-H bond in amine substrates via H-bonding, thus achieving the reductive transformation of CO2 to formamides, benzimidazoles, and benzothiazoles via cooperative catalysis. The second section describes our finding on the IL-catalyzed hydration of the C≡C bond in propargylic alcohols. Azolate anion-based ILs that can chemically capture CO2 via the formation of carbamates could serve as robust nucleophiles to attack the C≡C bond in propargylic alcohols and then efficiently catalyze the hydration of propargylic alcohols to produce α-hydroxy ketones with the assistance of atmospheric CO2 gas under metal-free conditions. The third section unveils the cooperative catalysis strategy of hydrogen bond donors and acceptors of ILs for chemical reactions. In the hydrogen-bonding catalysis protocols, cations of the ILs act as H-bond donors and anions, as acceptors, forming H-bonds with the reactant molecules, respectively, in opposite ways, which can cooperatively catalyze the ring-closing C-O/C-O bond metathesis reactions of aliphatic diethers to O-heterocycles, the dehydrative etherification of alcohols to ethers, and direct oxidative esterification of alcohols to esters. We believe that these IL-catalyzed metal-free processes and strategies display promising practical applications, and their commercialization would bring great benefits to the production of the as-afforded value-added chemicals.

Hydrogen bonding-catalysed alcoholysis of propylene oxide at room temperature

Alcoholysis of propylene oxide is achieved over azolate ionic liquids at room temperature by hydrogen-bonding catalysis, accessing glycol ethers in moderate to high yields with selectivity of >99%.

Computational Study on the Synergic Effect of Brønsted Acid and Hydrogen-Bonding Catalysis for the Dearomatization Reaction of Phenols with Diazo Functionality.

Catalytic dearomative transformations of phenol variants via an ipso-Friedel-Crafts reaction could provide a straightforward method for the rapid assembly of functionalized spiromolecules as versatile synthetic scaffolds. We previously reported a dearomative spirocyclization reaction by merging Brønsted acid and hydrogen-bonding catalysis. However, it was unclear how the reaction proceeded and how the synergic effect was triggered. Described herein are the computational studies used to elucidate the reaction mechanism. Such calculations indicated that the applied catalysts, maleic acid and Schreiner's thiourea, work cooperatively. The synergic effect enabled the chemoselectivity to interconvert between phenol dearomatization and O-H insertion, which is a major side reaction. This investigation also revealed that not only does the Schreiner's thiourea catalyst serve as a hydrogen bonding donor, but the sulfur atom in thiourea possesses a general base function. The dual functional support of the thiourea along with maleic acid would thus realize the chemoselective prioritization of dearomatization over the O-H insertion reaction under mild conditions.

Hydrogen-Bonding Catalysis of Alkyl-Onium Salts.

The synthetic utility of alkyl-onium salt compounds is widely recognized in the field of organic chemistry. Among the wide variety of onium salts, quaternary ammonium, phosphonium, and tertiary sulfonium salts have been the most useful compounds in organic syntheses. These compounds have been very useful reagents in the construction of organic building blocks. In addition, onium salts are known as reliable catalysts, which are used to promote important organic transformations by serving as phase-transfer and ion-pair catalysts through the activation of nucleophiles. Although phase-transfer catalysis is a major direction for onium salt catalysis, hydrogen-bonding catalysis of alkyl-onium salts, which is promoted via the activation of electrophiles, has recently become a relevant topic in the field of onium salt chemistry. This Minireview introduces new possibilities and future directions for alkyl-onium salt chemistry based on its use in hydrogen-bonding catalysis and on its overall utility.

Cooperative photoredox and chiral hydrogen-bonding catalysis

Chiral hydrogen-bonding catalysis is a classic strategy in asymmetric organocatalysis. Recently, it has been used to cooperate with photoredox catalysis, becoming a powerful tool to access optical pure compounds via radical-based transformations.