Salen Catalyst Research Articles

Practical Epoxidation of Olefins Using Air and Ubiquitous Iron-Based Fluorous Salen Complex.

The epoxidation of olefins by substituting "air" for potentially harmful oxidants was achieved using an oxidation method that integrated a fluorous iron(III) salen catalyst derived from common metals and pivalaldehyde. Several aromatic disubstituted olefins were converted into their corresponding epoxides with high efficiency and quantitative yields. This reaction represents an environmentally friendly oxidation process that utilizes an abundant source of air and employs a readily available metal, iron, in the form of salen complexes, making it an environmentally conscious oxidation reaction.

Oxidative cleavage of lignin model substrates with Co(salen) catalyst: an experimental study on the effect of different reaction parameters in batch and continuous flow

Continuous flow screening improved Co(salen)-catalyzed oxidative cleavage of lignin models, revealing new key parameters for robust and optimal batch operation.

Oxidative cleavage of β-O-4 bonds in lignin model compounds with polymer-supported Ni–Salen catalysts

The polymerized Salen-Ni(ii) complex can catalyze oxidative cleavage of the lignin model compounds into high-value aromatic chemicals without any base additive.

The metal role on the activity and stereoselectivity of ring opening polymerization of racemic lactide promoted by Salen catalysts

The stereoselective rac-lactide ring opening polymerization (ROP) promoted by enantiopure Salen catalysts has been studied by Density Functional Theory calculations with the aim of understanding the role of the metal atom in both the stereoselectivity and the activity of the process. The results obtained with M = Al, Sc, Y, La were compared to identify the steric and electronic effects deriving from the metal centre by combining a molecular descriptor based on the buried volume percentage (%VBur) and calculations of electronic parameters, including chemical hardness and electrophilicity. Our analysis gave insight into the parameters affecting the outcome of the ROP and we concluded that steric and electronic effects promoting stereoselective polymerization suppress catalyst activity and viceversa.

Metal-catalyzed copolymerizations of epoxides and carbon disulfide for high-refractive index low absorbance adhesives and plastics.

High-refractive index plastics are useful materials due to their optical properties, ease of processing, and low-costs compared to their inorganic counterparts. Catalytic carbon disulfide (CS2) copolymerization with epoxides is one method for producing low-cost high refractive index polymers. The reaction is accompanied by an oxygen-sulfur exchange reaction which produces irregular microstructures in the repeating units. In this study, metal salen catalysts were investigated with different metal centers (Al, Cr, Co) and salen ligand electronics, sterics, backbones, and co-catalyst in the copolymerization of CS2 with propylene oxide (PO) and cyclohexene oxide (CHO). The results reveal the essential nature of Cr metal centers on reactivity and the backbone geometry on monomer selectivity. There were no significant impacts on the O-S exchange reaction when ligand design changed, however PO and CHO/CS2 copolymers yield different monothiocarbonate microstructures. Additionally, the effects of microstructure on optical and thermal properties were investigated using spectroscopic ellipsometry and calorimetry, respectively. The CHO system produced high T g plastics (93°C) with high refractive indexes (n up to 1.64), modest absorbance (κ < 0.020), and Abbe numbers of 32.2 while PO yielded low T g adhesives (T g = 9°C) with high refractive indexes (n up to 1.73), low absorbance (κ < 0.005), and low Abbe numbers (V D = 19.1).

Synthesis, Thermal and Mechanical Properties of Linear and Star Poly(L‐lactide)s

AbstractPoly(L‐lactide) with various architectures and molecular weights have been studied with respect to their thermal and mechanical properties. Their synthesis has been performed with an aluminum salen catalyst, which allows to obtain linear chains, tetrahedral 4‐arm stars and stars with two linked tetrahedra with 3 arms each, all with defined molecular weights. The polymers are characterized by their molecular weight distributions and then subjected to differential scanning calorimetry and thermogravimetric analyses, which show differences in the characteristic temperatures of not more than 10 degrees. The crystallinity index clearly increases with the weight of the chains with only a minor dependency on the topology. Thin films of the polymers are studied with respect to their elongation at break, their tensile strength, and their moduli. The elongation is most sensitive to the polymer type with a 15‐fold increase between the shortest linear polymer and the 6‐arm star polymer with the longest chains.

Synthesis of Polyethylene Glycol-Poly(glycerol carbonate) Block Copolymeric Micelles as Surfactant-Free Drug Delivery Systems.

We report the synthesis of block copolymers of monomethoxylated polyethylene glycol and poly(glycerol carbonate) (mPEG-b-PGC) via the ring-opening polymerization of benzyl glycidyl ether, monomethoxylated polyethylene glycol, and carbon dioxide using a cobalt salen catalyst. The resulting block copolymers display high polymer/cyclic carbonate selectivity (>99%) and, if two oxirane monomers are used, random incorporation into the polymer feed. The resulting diblock mPEG-b-PGC polymer shows promise as a nanocarrier for surfactant-free, sustained chemotherapeutic delivery. mPEG-b-PGC, with paclitaxel conjugated to the pendant primary alcohol of the glycerol polymer backbone, readily forms 175 nm diameter particles in solution and contains 4.6 wt % paclitaxel (PTX), which is released over 42 days. The mPEG-b-PGC polymer itself is noncytotoxic, whereas the PTX-loaded nanoparticles are cytotoxic to lung, breast, and ovarian cancer cell lines.

Enantioselective radical cascade cyclization via Ti-catalyzed redox relay

Radical cascade cyclization reactions provide an efficient method for the construction of polycyclic architectures with multiple stereogenic centers. However, achieving enantioselectivity control of this type of reaction is a challenging task. Here, we report an enantioselective cyclization of polyfunctional aryl cyclopropyl ketone and alkyne units, wherein the stereochemical outcome is directed by a chiral Ti(salen) catalyst. This transformation was proposed to proceed via a radical cascade process involving the reductive ring-opening of the cyclopropyl ketone followed by two annulation events entailing cyclization of the ensuing alkyl radical onto the alkyne and subsequent addition of the incipient vinyl radical to the Ti(IV)-enolate.

Development and mechanistic investigation of the dehydrogenation of alcohols with an iron(III) salen catalyst.

The iron(III) salen complex (R,R)-N,N'-bis(salicylidene)-1,2-cyclohexanediamineiron(III) chloride has been developed as a catalyst for the acceptorless dehydrogenation of alcohols. The complex catalyzes the direct synthesis of imines in good yields from different primary alcohols and amines with the liberation of hydrogen gas. The mechanism has been investigated experimentally with labelled substrates and theoretically with density functional theory calculations. In contrast to the corresponding manganese(III) salen-catalyzed dehydrogenation, it has not been possible to identify a homogeneous catalytic pathway with the iron complex. Instead, poisoning experiments with trimethylphosphine and mercury indicated that the catalytically active species are heterogeneous small iron particles.

Enantioconvergent Benzylic C–H Azidation of Indolines Enabled by a Cationic Manganese Salen Catalyst

Key words azidation - indolines - manganese catalysis - salen ligands - tetrahydroquinones

Asymmetric Synthesis of Methoxylated Ether Lipids: A Glyceryl Glycidyl Ether Key Building Block Design, Preparation, and Synthetic Application.

The report describes the preparation and use of a double-C3 building block intended as a head group synthon in the synthesis of saturated, mono-, and polyunsaturated 1-O-alkyl-sn-glycerol type methoxylated ether lipids (MELs). The resulting head piece, an enantiopure isopropylidene-protected glyceryl glycidyl ether diastereomer, was accomplished in 49% yield (max 50%) from a 1:1 diastereomeric mixture obtained from R-solketal and racemic epichlorohydrin after treatment with the Jacobsen (S,S)-Co(III)salen catalyst for the hydrolytic kinetic resolution of terminal epoxides. The diol hydrolytic product obtained in 47% yield from the unwanted diastereomer was reconverted into epoxide with an inversion of configuration in a three-step operation involving a highly regioselective lipase. This enabled the recovery of a substantial amount of diastereopure material after a subsequent treatment with the Jacobsen catalyst to furnish the oxirane head piece in altogether 72% yield of higher than 99% diastereomeric purity. A modified synthesis of a monounsaturated 16:1 MEL confirmed the correct stereochemistry and excellent enantiopurity of the head piece and resulted in a dramatic improvement in yields, efficiency, and economy of the synthesis.

Cobalt-Catalyzed Cyclization of Unsaturated N-Acyl Sulfonamides: a Diverted Mukaiyama Hydration Reaction.

The cycloisomerization of β-, γ-, and δ-unsaturated N-acyl sulfonamides to N-sulfonyl lactams and imidates is reported. This transformation is effected in the presence of a CoIII(salen) catalyst using t-BuOOH or air as the oxidant. The method shows good functional group tolerance (alkyl, aryl, heteroaryl, ether, N-Boc) and furnishes an underexplored class of cyclic building blocks. The strong solvent dependence of the transformation is investigated, and the synthetic versatility of the N-sulfonyl imidate product class is highlighted.

Cobalt‐Catalyzed Intermolecular Hydroamination of Unactivated Alkenes Using NFSI as Nitrogen Source

Comprehensive SummaryCheap metal (Fe, Mn, and Co)‐catalyzed hydroamination of alkenes has been an attractive method for synthesis of amines because of biocompatibility of metal, excellent Markovnikov selectivity and chemoselectivity. However, most reports are limited to unsaturated nitrogen sources (nitric oxide, azos, azides, cyano, etc.), for which aminated products are very limited. Notably, while used widely for fluorinating reaction, N‐fluorobenzenesulfonimide (NFSI) as amine source for hydroamination has seldom been reported. Here we developed a cobalt‐catalyzed intermolecular hydroamination of unactivated alkenes using NFSI as nitrogen source under mild conditions. The reaction exhibits excellent chemo‐ and regio‐selectivity with no hydrofluorination or linear‐selectivity products. Notably, the reaction proceeded with excellent yield even though the amount of Co(salen) catalyst was reduced to 0.2 mol%. Recently, a similar work was also reported by Zhang and coworkers (ref. 19).

Controlled release of 5-Fluorouracil by a novel L-Lysine based polyesterurethane material synthesized from Epoxide and CO2 via a novel dicopper salen catalyst

Controlled release of anticancer drug 5-Fluorouracil by several delivery systems are known including porous polymeric materials. Herein we report a novel L-lysine based porous polyesterurethane material 1 which acts as a controlled release vehicle for 5-Fluorouracil. Polyesterurethane material 1 was synthesized from a green isocyanate and phosgene free synthetic route involving conversion of epoxide 2-(phenoxymethyl)oxirane and CO2 to cyclic carbonate 2 followed by ring opening with an amino acid L-Lysine to a bishydroxy compound 3 under green aqueous reaction condition. The bishydroxy compound 3 was subsequently reacted with 0.66 equivalent of trimesyl chloride in presence of triethyl amine to get the polyesterurethane material 1. The polyesterurethane material 1 was characterized via NMR, IR and MALDI analysis. From the SEM image of the polyesterurethane 1 and 5-Fluorouracil encapsulated polyesterurethane 1 it is evident that material 1 remain with porous topology which is filled by 5-Fluorouracil that is further evidenced by EDX spectroscopy with the presence of Fluorine. The controlled release of 5-Fluorouracil from the drug encapsulated 1 was monitored via UV visible spectroscopy at pH 7.4.

Cobalt-Catalyzed Radical Hydroamination of Alkenes with N-Fluorobenzenesulfonimides.

An efficient and general radical hydroamination of alkenes using Co(salen) as catalyst, N-fluorobenzenesulfonimide (NFSI) and its analogues as both nitrogen source and oxidant was successfully disclosed. A variety of alkenes, including aliphatic alkenes, styrenes, α, β-unsaturated esters, amides, acids, as well as enones, were all compatible to provide desired amination products. Mechanistic experiments suggest that the reaction underwent a metal-hydride-mediated hydrogen atom transfer (HAT) with alkene, followed by a pivotal catalyst controlled SN 2-like pathway between in situ generated organocobalt(IV) species and nitrogen-based nucleophiles. Moreover, by virtue of modified chiral cobalt(II)-salen catalyst, an unprecedented asymmetric version was also achieved with good to excellent level of enantiocontrol. This novel asymmetric radical C-N bond construction opens a new door for the challenging asymmetric radical hydrofunctionalization.

Cobalt‐Catalyzed Radical Hydroamination of Alkenes with N‐Fluorobenzenesulfonimides

AbstractAn efficient and general radical hydroamination of alkenes using Co(salen) as catalyst, N‐fluorobenzenesulfonimide (NFSI) and its analogues as both nitrogen source and oxidant was successfully disclosed. A variety of alkenes, including aliphatic alkenes, styrenes, α, β‐unsaturated esters, amides, acids, as well as enones, were all compatible to provide desired amination products. Mechanistic experiments suggest that the reaction underwent a metal‐hydride‐mediated hydrogen atom transfer (HAT) with alkene, followed by a pivotal catalyst controlled SN2‐like pathway between in situ generated organocobalt(IV) species and nitrogen‐based nucleophiles. Moreover, by virtue of modified chiral cobalt(II)‐salen catalyst, an unprecedented asymmetric version was also achieved with good to excellent level of enantiocontrol. This novel asymmetric radical C−N bond construction opens a new door for the challenging asymmetric radical hydrofunctionalization.

Two‐Step Access toβ‐Substitutedo‐Hydroxyphenyl Ethyl Ketones from 4‐Chromanone and its Application in Preparation of a Silica‐Supported Cobalt(II) Salen Complex

AbstractTheo‐hydroxyphenyl ethyl ketone skeleton is prevalent in many biologically active natural products and active pharmaceutical ingredients. Herein, a two‐step protocol has been developed for synthesis of variousβ‐substitutedo‐hydroxyphenyl ethyl ketones. A base‐mediated ring opening of 4‐chromanone was used to introduce theβ‐ethoxylo‐hydroxyphenyl ethyl ketone intermediary, followed by nucleophile substitution under BF3 ⋅ Et2O assisted conditions to give the desiredβ‐carbon, nitrogen, or thiol substitutedo‐hydroxyphenyl ethyl ketones. With the aid of this protocol, a silica‐supported cobalt(II) salen complex was successfully prepared and its structure was confirmed by FTIR,13C MAS NMR, UV‐Vis absorption, and XPS spectra. The immobilized cobalt(II) salen catalyst not only displayed comparable catalytic activity in the synthesis of several heterocycles including 1,3‐oxazolidine, benzimidazole, and benzoxazole as compared with their homogeneous counterparts, but also could be recycled for several times without obvious loss of its catalytic activity.magnified image

Chirality-Directed Regioselectivity: An Approach for the Synthesis of Alternating Poly(Lactic-co-Glycolic Acid).

We report the synthesis of alternating poly(lactic-co-glycolic acid) via a regioselective ring-opening polymerization of (S)-methyl glycolide. An enantiopure aluminum salen catalyst with binaphthyl backbone facilitates the regioselective ring-opening of this unsymmetrical cyclic diester exclusively at the glycolide acyl-oxygen bond site. This living, chain-growth polymerization is able to reach low dispersities with tailored molecular weights. Quantitative regioselectivity calculations and sequence error analysis have been established for this sequence-controlled polymer.

Recent development of magnetic nanomaterial-supported M(Salen) composites as recyclable heterogeneous catalysts

Metal complexes of Salen-type ligands [M(Salen)] were widely used as catalysts with high activity for coupling reactions, addition reactions and epoxidation reactions. However, homogeneous catalysts based on M(Salen) complexes are difficult to separate and recover. Therefore, it is of great significance to find suitable supports to support M(Salen) complexes and obtain composites as separable and recyclable heterogeneous catalysts. Magnetic nanomaterials, which is widely researched as an inorganic nanosupports, are advantageous for the preparation of supported M(Salen) catalysts due to their characteristics of magnetic separation, good chemical stability and easy functionalization. In this review, research works on many types of the magnetic nanomaterial-supported M(Salen) catalysts, especially their preparations and applications as heterogeneous catalysts are discussed in detail. In addition, the advantages and disadvantages of different magnetic nanomaterials-supported M(Salen) composites are described, and some recommendations and references are provided for structure design of magnetic nanomaterial-supported M(Salen) catalyst with improved magnetic separation and catalytic efficiency. At last, limitations of magnetic nanomaterial-supported M(Salen), including structural instability, tedious multistep reactions and difficulty in industrial production, are discussed and their applications as heterogeneous catalysts are prospected.

Mechanistic Studies Inform Design of Improved Ti(salen) Catalysts for Enantioselective [3 + 2] Cycloaddition.

Ti(salen) complexes catalyze the asymmetric [3 + 2] cycloaddition of cyclopropyl ketones with alkenes. While high enantioselectivities are achieved with electron-rich alkenes, electron-deficient alkenes are less selective. Herein, we describe mechanistic studies to understand the origins of catalyst and substrate trends in an effort to identify a more general catalyst. Density functional theory (DFT) calculations of the selectivity determining transition state revealed the origin of stereochemical control to be catalyst distortion, which is largely influenced by the chiral backbone and adamantyl groups on the salicylaldehyde moieties. While substitution of the adamantyl groups was detrimental to the enantioselectivity, mechanistic information guided the development of a set of eight new Ti(salen) catalysts with modified diamine backbones. These catalysts were evaluated with four electron-deficient alkenes to develop a three-parameter statistical model relating enantioselectivity to physical organic parameters. This statistical model is capable of quantitative prediction of enantioselectivity with structurally diverse alkenes. These mechanistic insights assisted the discovery of a new Ti(salen) catalyst, which substantially expanded the reaction scope and significantly improved the enantioselectivity of synthetically interesting building blocks.