Brønsted acid catalysis of photosensitized cycloadditions

Catalysis is central to contemporary synthetic chemistry. There has been a recent recognition that the rates of photochemical reactions can be profoundly impacted by the use of Lewis acid catalysts and co-catalysts. Herein, we show that Brønsted acids can also modulate the reactivity of excited-state organic reactions. Brønsted acids dramatically increase the rate of Ru(bpy)₃²⁺-sensitized [2 + 2] photocycloadditions between C-cinnamoyl imidazoles and a range of electron-rich alkene reaction partners. A combination of experimental and computational studies supports a mechanism in which the Brønsted acid co-catalyst accelerates triplet energy transfer from the excited-state [Ru*(bpy)₃]²⁺ chromophore to the Brønsted acid activated C-cinnamoyl imidazole. Computational evidence further suggests the importance of driving force as well as geometrical reorganization, in which the protonation of the imidazole decreases the reorganization penalty during the energy transfer event.

Brønsted acids can catalyze triplet energy transfer reactions, and DFT computations suggest the unexpected importance of reorganization energy for catalysis.     

A Comprehensive Investigation of the Structural,Thermal, and Biological Properties of Fully Randomized Biomedical Polyesters Synthesized with a Nontoxic Bismuth(III) Catalyst

Aliphatic polyesters are the most common type of biodegradable synthetic polymer used in many pharmaceutical applications nowadays. This report describes the ring-opening polymerization (ROP) of l-lactide (L-LA), ε-caprolactone (CL) and glycolide (Gly) in the presence of a simple, inexpensive and convenient PEG200-BiOct₃ catalytic system. The chemical structures of the obtained copolymers were characterized by ¹H- or ¹³C-NMR. GPC was used to estimate the average molecular weight of the resulting polyesters, whereas TGA and DSC were employed to determine the thermal properties of polymeric products. The effects of temperature, reaction time, and catalyst content on the polymerization process were investigated. Importantly, the obtained polyesters were not cyto- or genotoxic, which is significant in terms of the potential for medical applications (e.g., for drug delivery systems). As a result of transesterification, the copolymers obtained had a random distribution of comonomer units along the polymer chain. The thermal analysis indicated an amorphous nature of poly(l-lactide-co-ε-caprolactone) (PLACL) and a low degree of crystallinity of poly(ε-caprolactone-co-glycolide) (PCLGA, X_c = 15.1%), in accordance with the microstructures with random distributions and short sequences of comonomer units (l = 1.02–2.82). Significant differences in reactivity were observed among comonomers, confirming preferential ring opening of L-LA during the copolymerization process.     

Cooperative activating effects of metal ion and Brønsted acid on a metal oxo species

Metal oxo (M O) complexes are common oxidants in chemical and biological systems. The use of Lewis acids to activate metal oxo species has attracted great interest in recent years, especially after the discovery of the CaMn₄O₅ cluster in the oxygen-evolving centre of photosystem II. Strong Lewis acids such as Sc³⁺ and BF₃, as well as strong Brønsted acids such as H₂SO₄ and CF₃SO₃H, are commonly used to activate metal oxo species. In this work, we demonstrate that relatively weak Lewis acids such as Ca²⁺ and other group 2 metal ions, as well as weak Brønsted acids such as CH₃CO₂H, can readily activate the stable RuO₄⁻ complex towards the oxidation of alkanes. Notably, the use of Ca²⁺ and CH₃CO₂H together produces a remarkable cooperative effect on RuO₄⁻, resulting in a much more efficient oxidant. DFT calculations show that Ca²⁺ and CH₃CO₂H can bind to two oxo ligands to form a chelate ring. This results in substantial lowering of the barrier for hydrogen atom abstraction from cyclohexane.

Combining a weak Lewis acid and weak Brønsted acid produces strong cooperative effects for activating metal oxo species towards alkane oxidation.     

Synthesis of [B,Al]-EWT-Type Zeolite and Its Catalytic Properties

EWT zeolite belongs to ultra-large pore zeolite with the 10MR and 21MR channels, which has good thermal stability, certain acid strength and good application prospects in petroleum refining and petrochemical reactions. However, EWT zeolite has fewer medium/strong acid sites, especially Brönsted acid sites, which makes it difficult to apply to acid-catalyzed reactions. The regulation of acid amount and distribution was achieved by boron and aluminum substitution into the siliceous framework of EWT. The physico-chemical properties of the samples were characterized by XRD, SEM, N₂ adsorption-desorption, XRF, ICP, Py-IR, NH₃-TPD and ¹¹B & ²⁷Al & ²⁹Si MAS NMR. The results show that quantities of boron and aluminum elements can occupy the framework of [B,Al]-EWT to increase the density of medium and strong acid centers, with more acidity and Brönsted acid centers than EWT zeolite. In the reaction of glycerol with cyclohexanone, the conversion of the sample (U-90-08-10/U-90-H-HCl) is significantly higher than that of the EWT sample, approaching or exceeding the Beta zeolite. A catalytic activity study revealed a direct correlation between the Brönsted acidic site concentration and the activity of the catalyst. The U-90-08-10-H catalyst was also considerably stable in the catalytic process. This work shows, for the first time, that extra-large pore zeolites can be used in industrial acid-catalytic conversion processes with excellent catalytic performance.     

Biomimetic hydrogen-bonding cascade for chemical activation: telling a nucleophile from a base

Hydrogen bonding-assisted polarization is an effective strategy to promote bond-making and bond-breaking chemical reactions. Taking inspiration from the catalytic triad of serine protease active sites, we have devised a conformationally well-defined benzimidazole platform that can be systematically functionalized to install multiple hydrogen bonding donor (HBD) and acceptor (HBA) pairs in a serial fashion. We found that an increasing number of interdependent and mutually reinforcing HBD–HBA contacts facilitate the bond-forming reaction of a fluorescence-quenching aldehyde group with the cyanide ion, while suppressing the undesired Brønsted acid–base reaction. The most advanced system, evolved through iterative rule-finding studies, reacts rapidly and selectively with CN⁻ to produce a large (>180-fold) enhancement in the fluorescence intensity at λ_max = 450 nm.

Biomimetic cascade hydrogen bonds promote covalent capture of a nucleophile by polarizing the electrophilic reaction site, while suppressing non-productive acid–base chemistry as the competing reaction pathway.     

Brønsted acid-mediated ring-opening reactions of methylenecyclopropanes: a dramatic counter ion effect

We report herein two different ring-opening patterns of methylenecyclopropanes (MCPs) in the presence of two Brønsted acids heptadecafluorooctane-1-sulfonic acid (C₈F₁₇SO₃H) and toluene p-sulfonic acid (TsOH) under mild conditions: (a) the ring-opening of MCPs by H₂O and subsequent etherification give the corresponding homoallylic ethers in the presence of heptadecafluorooctane-1-sulfonic acid; (b) the direct ring-opening of MCPs by the Brønsted acid gives the corresponding homoallylic alcohol derivatives in the presence of toluene p-sulfonic acid.     

Tailoring Lewis/Brønsted acid properties of MOF nodes via hydrothermal and solvothermal synthesis: simple approach with exceptional catalytic implications

The Lewis/Brønsted catalytic properties of the Metal–Organic Framework (MOF) nodes can be tuned by simply controlling the solvent employed in the synthetic procedure. In this work, we demonstrate that Hf-MOF-808 can be prepared from a material with a higher amount of Brønsted acid sites, via modulated hydrothermal synthesis, to a material with a higher proportion of unsaturated Hf Lewis acid sites, via modulated solvothermal synthesis. The Lewis/Brønsted acid properties of the resultant metallic clusters have been studied by different characterization techniques, including XAS, FTIR and NMR spectroscopies, combined with a DFT study. The different nature of the Hf-MOF-808 materials allows their application as selective catalysts in different target reactions requiring Lewis, Brønsted or Lewis–Brønsted acid pairs.

The Brønsted/Lewis acid properties of Hf-MOF-808 can be tuned by simply controlling the solvent employed in its synthesis, with direct catalytic implications on the activity and selectivity of organic reactions sensitive to the active site nature.     

Photocatalyst-independent photoredox ring-opening polymerization of O-carboxyanhydrides: stereocontrol and mechanism

Photoredox ring-opening polymerization of O-carboxyanhydrides allows for the synthesis of polyesters with precisely controlled molecular weights, molecular weight distributions, and tacticities. While powerful, obviating the use of precious metal-based photocatalysts would be attractive from the perspective of simplifying the protocol. Herein, we report the Co and Zn catalysts that are activated by external light to mediate efficient ring-opening polymerization of O-carboxyanhydrides, without the use of exogenous precious metal-based photocatalysts. Our methods allow for the synthesis of isotactic polyesters with high molecular weights (>200 kDa) and narrow molecular weight distributions (M_w/M_n < 1.1). Mechanistic studies indicate that light activates the oxidative status of a Co^III intermediate that is generated from the regioselective ring-opening of the O-carboxyanhydride. We also demonstrate that the use of Zn or Hf complexes together with Co can allow for stereoselective photoredox ring-opening polymerizations of multiple racemic O-carboxyanhydrides to synthesize syndiotactic and stereoblock copolymers, which vary widely in their glass transition temperatures.

Photoredox ring-opening polymerization of O-carboxyanhydrides allows for the synthesis of functionalized polyesters with high molecular weights, narrow molecular weight distributions, and various tacticities.     

Catalytic asymmetric transformations of racemic α-borylmethyl-(E)-crotylboronate via kinetic resolution or enantioconvergent reaction pathways

We report herein catalytic asymmetric transformations of racemic α-borylmethyl-(E)-crotylboronate. The Brønsted acid-catalyzed kinetic resolution–allylboration reaction sequence of the racemic reagent gave (Z)-δ-hydroxymethyl-anti-homoallylic alcohols with high Z-selectivities and enantioselectivities upon oxidative workup. In parallel, enantioconvergent pathways were utilized to synthesize chiral nonracemic 1,5-diols and α,β-unsaturated aldehydes with excellent optical purity.

We report herein catalytic asymmetric transformations of racemic α-borylmethyl-(E)-crotylboronate.     

How to not build a cage: endohedral functionalization of polyoxometalate-based metal–organic polyhedra

Introducing functionalities into the interior of metal–organic cage complexes can confer properties and utilities (e.g. catalysis, separation, drug delivery, and guest recognition) that are distinct from those of unfunctionalized cages. Endohedral functionalization of such cage molecules, for decades, has largely relied on modifying their organic linkers to covalently append targeted functional groups to the interior surface. We herein introduce an effective coordination method to bring in functionalities at the metal sites instead, for a set of polyhedral cages where the nodes are in situ formed polyoxovanadate clusters, [V^IV₆O₆(OCH₃)₉(μ₆-SO₄)(COO)₃]²⁻. Replacing the central sulfates of these hexavanadate clusters with more strongly coordinating phosphonate groups allows the installation of functionalities within the cage cavities. Organophosphonates with phenyl, biphenyl, and terphenyl tails were examined for internalization. Depending on the size/shape of the cavities, small phosphonates can fit into the molecular containers whereas larger ones inhibit or transform the framework architecture, whereby the first non-cage complex was isolated from a reaction that otherwise would lead to entropically favored regular polyhedra cages. The results highlight the complex and dynamic nature of the self-assembly process involving polyoxometalates and the scope of molecular variety accessible by the introduction of endo functional groups.

Installation of oversized functions within a metal–organic cage may “burst” or even transform the molecular cage itself.     

Encapsulation of tricopper cluster in a synthetic cryptand enables facile redox processes from CuICuICuI to CuIICuIICuII states

One-pot reaction of tris(2-aminoethyl)amine (TREN), [Cu^I(MeCN)₄]PF₆, and paraformaldehyde affords a mixed-valent [TREN₄Cu^IICu^ICu^I(μ₃-OH)](PF₆)₃ complex. The macrocyclic azacryptand TREN₄ contains four TREN motifs, three of which provide a bowl-shape binding pocket for the [Cu₃(μ₃-OH)]³⁺ core. The fourth TREN caps on top of the tricopper cluster to form a cryptand, imposing conformational constraints and preventing solvent interaction. Contrasting the limited redox capability of synthetic tricopper complexes reported so far, [TREN₄Cu^IICu^ICu^I(μ₃-OH)](PF₆)₃ exhibits several reversible single-electron redox events. The distinct electrochemical behaviors of [TREN₄Cu^IICu^ICu^I(μ₃-OH)](PF₆)₃ and its solvent-exposed analog [TREN₃Cu^IICu^IICu^II(μ₃-O)](PF₆)₄ suggest that isolation of tricopper core in a cryptand enables facile electron transfer, allowing potential application of synthetic tricopper complexes as redox catalysts. Indeed, the fully reduced [TREN₄Cu^ICu^ICu^I(μ₃-OH)](PF₆)₂ can reduce O₂ under acidic conditions. The geometric constraints provided by the cryptand are reminiscent of Nature''s multicopper oxidases (MCOs). For the first time, a synthetic tricopper cluster was isolated and fully characterized at Cu^ICu^ICu^I (4a), Cu^IICu^ICu^I (4b), and Cu^IICu^IICu^I (4c) states, providing structural and spectroscopic models for many intermediates in MCOs. Fast electron transfer rates (10⁵ to 10⁶ M⁻¹ s⁻¹) were observed for both Cu^ICu^ICu^I/Cu^IICu^ICu^I and Cu^IICu^ICu^I/Cu^IICu^IICu^I redox couples, approaching the rapid electron transfer rates of copper sites in MCO.

Geometric constraints and site isolation provided by the cryptand enable reversible redox of tricopper μ-oxo cluster.     

Probing the electronic and mechanistic roles of the μ4-sulfur atom in a synthetic CuZ model system

Nitrous oxide (N₂O) contributes significantly to ozone layer depletion and is a potent greenhouse agent, motivating interest in the chemical details of biological N₂O fixation by nitrous oxide reductase (N₂OR) during bacterial denitrification. In this study, we report a combined experimental/computational study of a synthetic [4Cu:1S] cluster supported by N-donor ligands that can be considered the closest structural and functional mimic of the Cu_Z catalytic site in N₂OR reported to date. Quantitative N₂ measurements during synthetic N₂O reduction were used to determine reaction stoichiometry, which in turn was used as the basis for density functional theory (DFT) modeling of hypothetical reaction intermediates. The mechanism for N₂O reduction emerging from this computational modeling involves cooperative activation of N₂O across a Cu/S cluster edge. Direct interaction of the μ₄-S ligand with the N₂O substrate during coordination and N–O bond cleavage represents an unconventional mechanistic paradigm to be considered for the chemistry of Cu_Z and related metal–sulfur clusters. Consistent with hypothetical participation of the μ₄-S unit in two-electron reduction of N₂O, Cu K-edge and S K-edge X-ray absorption spectroscopy (XAS) reveal a high degree of participation by the μ₄-S in redox changes, with approximately 21% S 3p contribution to the redox-active molecular orbital in the highly covalent [4Cu:1S] core, compared to approximately 14% Cu 3d contribution per copper. The XAS data included in this study represent the first spectroscopic interrogation of multiple redox levels of a [4Cu:1S] cluster and show high fidelity to the biological Cu_Z site.

Experimental data and computational modeling indicates an active role for the bridging sulfide ligand in a synthetic Cu_Z model.     

Highly enantioselective sulfa-Michael addition reactions using N-heterocyclic carbene as a non-covalent organocatalyst

We report the first asymmetric sulfa-Michael addition (SMA) reactions using a chiral N-heterocyclic carbene (NHC) as a non-covalent organocatalyst. We demonstrate that a triazolium salt derived NHC functions as an excellent Brønsted base to promote enantioselective carbon–sulfur bond formation. The reaction is applicable to a wide range of thiols and electrophilic olefins. Notably, quaternary chiral centers bearing both an S atom and a CF₃ group were synthesized with excellent asymmetric control. Mechanistic studies suggest that the facial discrimination is likely to be guided by non-covalent interactions: hydrogen bonding and π–π stacking.     

Combining alkali metals and zinc to harness heterometallic cooperativity in cyclic ester ring-opening polymerisation

Heterometallic cooperativity is an emerging strategy to elevate polymerisation catalyst performance. Here, we report the first heterotrimetallic Na/Zn₂ and K/Zn₂ complexes supported by a ProPhenol ligand, which deliver “best of both” in cyclic ester ring-opening polymerisation, combining the outstanding activity (Na/K) and good control (Zn₂) of homometallic analogues. Detailed NMR studies and density-functional theory calculations suggest that the Na/Zn₂ and K/Zn₂ complexes retain their heterometallic structures in the solution-state. To the best of our knowledge, the K/Zn₂ analogue is the most active heterometallic catalyst reported for rac-lactide polymerisation (k_obs = 1.7 × 10⁻² s⁻¹), giving activities five times faster than the Na/Zn₂ complex. These versatile catalysts also display outstanding performance in ε-caprolatone and δ-valerolactone ring-opening polymerisation. These studies provide underpinning methodologies for future heterometallic polymerisation catalyst design, both in cyclic ester polymerisation and other ring-opening (co)polymerisation reactions.

Cooperative heterotrimetallic Na/Zn₂ and K/Zn₂ complexes combine the excellent activities and control of the homometallic analogues, giving “best of both” in cyclic ester ring-opening polymerisation.     

On the Role of Protonic Acid Sites in Cu Loaded FAU31 Zeolite as a Catalyst for the Catalytic Transformation of Furfural to Furan

The aim of the present paper is to study the speciation and the role of different active site types (copper species and Brønsted acid sites) in the direct synthesis of furan from furfural catalyzed by copper-exchanged FAU31 zeolite. Four series of samples were prepared by using different conditions of post-synthesis treatment, which exhibit none, one or two types of active sites. The catalysts were characterized by XRD, low-temperature sorption of nitrogen, SEM, H₂-TPR, NMR and by means of IR spectroscopy with ammonia and CO sorption as probe molecules to assess the types of active sites. All catalyst underwent catalytic tests. The performed experiments allowed to propose the relation between the kind of active centers (Cu or Brønsted acid sites) and the type of detected products (2-metylfuran and furan) obtained in the studied reaction. It was found that the production of 2-methylfuran (in trace amounts) is determined by the presence of the redox-type centers, while the protonic acid sites are mainly responsible for the furan production and catalytic activity in the whole temperature range. All studied catalysts revealed very high susceptibility to coking due to polymerization of furfural.     

Structural elucidation of a methylenation reagent of esters: synthesis and reactivity of a dinuclear titanium(iii) methylene complex

Transmetallation of a zinc methylene complex [ZnI(tmeda)]₂(μ-CH₂) with a titanium(iii) chloride [TiCl₃(tmeda)(thf)] produced a titanium methylene complex. The X-ray diffraction study displayed a dinuclear methylene structure [TiCl(tmeda)]₂(μ-CH₂)(μ-Cl)₂. Treatment of an ester with the titanium methylene complex resulted in methylenation of the ester carbonyl to form a vinyl ether. The titanium methylene complex also reacted with a terminal olefin, resulting in olefin-metathesis and olefin-homologation. Cyclopropanation by methylene transfer from the titanium methylene proceeded by use of a 1,3-diene. The mechanistic study of the cyclopropanation reaction by the density functional theory calculations was also reported.

Transmetallation of a zinc methylene complex [ZnI(tmeda)]₂(μ-CH₂) with a titanium(iii) chloride [TiCl₃(tmeda)(thf)] produced a titanium methylene complex.     

Carbon monoxide and hydrogen (syngas) as a C1-building block for selective catalytic methylation

A catalytic reaction using syngas (CO/H₂) as feedstock for the selective β-methylation of alcohols was developed whereby carbon monoxide acts as a C1 source and hydrogen gas as a reducing agent. The overall transformation occurs through an intricate network of metal-catalyzed and base-mediated reactions. The molecular complex [Mn(CO)₂Br[HN(C₂H₄PⁱPr₂)₂]] 1 comprising earth-abundant manganese acts as the metal component in the catalytic system enabling the generation of formaldehyde from syngas in a synthetically useful reaction. This new syngas conversion opens pathways to install methyl branches at sp³ carbon centers utilizing renewable feedstocks and energy for the synthesis of biologically active compounds, fine chemicals, and advanced biofuels.

A broadly applicable catalytic process for the selective β-methylation of alcohols is presented using syngas (CO/H₂) directly as a C1 building block and the shown manganese complex in the presence of a base as the catalytic system.     

Synergistic Brønsted/Lewis acid catalyzed aromatic alkylation with unactivated tertiary alcohols or di-tert-butylperoxide to synthesize quaternary carbon centers

Dual Brønsted/Lewis acid catalysis involving environmentally benign, readily accessible protic acid and iron promotes site-selective tert-butylation of electron-rich arenes using di-tert-butylperoxide. This transformation inspired the development of a synergistic Brønsted/Lewis acid catalyzed aromatic alkylation that fills a gap in the Friedel–Crafts reaction literature by employing unactivated tertiary alcohols as alkylating agents, leading to new quaternary carbon centers. Corroborated by DFT calculations, the Lewis acid serves a role in enhancing the acidity of the Brønsted acid. The use of non-allylic, non-benzylic, and non-propargylic tertiary alcohols represents an underexplored area in Friedel–Crafts reactivity.

Dual Brønsted/Lewis acid catalysis involving environmentally benign, readily accessible protic acid and iron promotes site-selective tert-alkylation of arenes using di-tert-butylperoxide and tertiary alcohols.     

The role of neutral donor ligands in the isoselective ring-opening polymerization of rac-β-butyrolactone

Isoenriched poly-3-hydroxybutyrate (P3HB) is a biodegradable material with properties similar to isotactic polypropylene, yet efficient routes to this material are lacking after 50+ years of extensive efforts in catalyst design. In this contribution, a novel lanthanum aminobisphenolate catalyst (1-La) can access isoenriched P3HB through the stereospecific ring-opening polymerization (ROP) of rac-β-butyrolactone (rac-BBL). Replacing the tethered donor group of a privileged supporting ligand with a non-coordinating benzyl substituent generates a catalyst whose reactivity and selectivity can be tuned with inexpensive achiral neutral donor ligands (e.g. phosphine oxides, OPR₃). The 1-La/OPR₃ (R = n-octyl, Ph) systems display high activity and are the most isoselective homogeneous catalysts for the ROP of rac-BBL to date (0 °C: P_m = 0.8, TOF ∼190 h⁻¹). Combined reactivity and spectroscopic studies provide insight into the active catalyst structure and ROP mechanism. Both 1-La(TPPO)2 and a structurally related catalyst with a tethered donor group (2-Y) operate under chain-end stereocontrol; however, 2-RE favors formation of P3HB with opposite tacticity (syndioenriched) and its ROP activity and selectivity are totally unaffected by added neutral donor ligands. Our studies uncover new roles for neutral donor ligands in stereospecific ROP, including suppression of chain-scission events, and point to new opportunities for catalyst design.

Simple achiral neutral donor ligands modify catalyst structure and function to enable access to isoenriched poly-3-hydroxybutyrate, a biodegradable material with properties similar to isotactic polypropylene.     

Ti-catalyzed ring-opening oxidative amination of methylenecyclopropanes with diazenes

The ring-opening oxidative amination of methylenecyclopropanes (MCPs) with diazenes catalyzed by py₃TiCl₂(NR) complexes is reported. This reaction selectively generates branched α-methylene imines as opposed to linear α,β-unsaturated imines, which are difficult to access via other methods. Products can be isolated as the imine or hydrolyzed to the corresponding ketone in good yields. Mechanistic investigation via density functional theory suggests that the regioselectivity of these products results from a Curtin–Hammett kinetic scenario, where reversible β-carbon elimination of a spirocyclic [2 + 2] azatitanacyclobutene intermediate is followed by selectivity-determining β-hydrogen elimination of the resulting metallacycle. Further functionalizations of these branched α-methylene imine products are explored, demonstrating their utility as building blocks.

The ring-opening oxidative amination of methylenecyclopropanes (MCPs) with diazenes catalyzed by py₃TiCl₂(NR) complexes is reported.