Synthesis of Pyrrolizidine,Indolizidine, and Quinolizidine Derivatives Using Ruthenium‐Catalyzed Ring‐Opening Metathesis and Ring‐Closing Metathesis of Cycloalkene‐ynes

Ring‐opening metathesis and ring‐closing metathesis (ROM‐RCM) of a cyclopentene‐yne having an ester moiety was demonstrated using first‐ and second‐generation Grubbs’ catalysts. When the reaction of cycloalkene‐yne was carried out in the presence of 5 mol % of a ruthenium carbene complex under an ethylene atmosphere at room temperature, ROM‐RCM proceeded smoothly to give a pyrrolidine derivative in good yield, which could be converted to a pyrrolizidine derivative. Furthermore, ROM‐RCM of azabicyclo[2.2.1]heptene‐ynes using the second‐generation Grubbs’ catalyst was investigated. When an azabicycloheptene derivative was exposed to a catalytic amount of a ruthenium carbene complex, pyrrolizidine and indolizidine derivatives were obtained in good yields. The distribution of these products depends on the substituents on the alkyne. When azabicyclo[2.2.1]heptene‐ynes bearing large substituents on the alkyne were treated with ruthenium catalyst 1b , a pyrrolizidine derivative was obtained as the major product. ROM‐RCM of azabicyclo[2.2.2]octene‐ynes with 1b afforded quinolizidine derivative 20 , although the yield was moderate.     

New Indenylidene‐Schiff Base‐Ruthenium Complexes for Cross‐Metathesis and Ring‐Closing Metathesis

We here report on the stability and catalytic activity of new indenylidene‐Schiff base‐ruthenium complexes 3a – f through representative cross‐metathesis (CM) and ring‐closing metathesis (RCM) reactions. Excellent activity of the new complexes was found for the two selected RCM reactions; prominent conversion was obtained compared to the commercial Hoveyda–Grubbs catalyst 2 . Moreover, excellent results were obtained for a standard CM reaction. Higher conversions were achieved with one of the indenylidene catalysts compared with Hoveyda–Grubbs catalyst. Unexpectedly, an isomerization reaction was observed during the CM reaction of allylbenzene. To the best of our knowledge, isomerization reactions in this model CM reaction in closed systems have never been described using first generation catalysts, including the Hoveyda–Grubbs catalyst. The first model CM reactions as well as the RCM reactions have been monitored using ¹H NMR. The course of the CM reaction of 3‐phenylprop‐1‐ene ( 8 ) and cis‐1,4‐diacetoxybut‐2‐ene ( 9 ) was monitored by GC. The isomerization reaction was studied by means of GC‐mass spectrometry and in situ IR spectroscopy. All catalysts were structurally characterized by means of ¹H, ¹³C, and ³¹P NMR spectroscopy.     

Mesocellular Foam‐Supported Catalysts: Enhanced Activity and Recyclability for Ring‐Closing Metathesis

Although ring‐closing metathesis (RCM) has been one of the most powerful methodologies for creating cyclic compounds, the pharmaceutical industry has not yet widely adopted this process commercially due to the high costs and leaching problems of homogeneous ruthenium catalysts. To circumvent these problems, we have immobilized the second‐generation Hoveyda–Grubbs catalyst effectively onto siliceous mesocellular foam (MCF). The open and interconnected pores of MCF facilitated ligand immobilization and substrate diffusion. We have observed that the ligand and metal loadings significantly affected the catalytic activity and recyclability. Enhanced recyclability by suppression of ruthenium leaching was achieved by using excess immobilized ligands. The resulting novel heterogenized catalysts demonstrated excellent activity and reusability for the RCM of various types of substrates.     

Formation of Arenes via Diallylarenes: Strategic Utilization of Suzuki–Miyaura Cross‐Coupling,Claisen Rearrangement and Ring‐Closing Metathesis

Two new synthetic strategies for benzoannulation are reported. The first strategy is based on the Suzuki–Miyaura cross‐coupling reaction. To this end, various ortho‐diallylbenzene derivatives were prepared from the corrresponding diiodo derivatives by an allylation strategy using an allylboronate as coupling partner. These diallyl derivatives were subjected to a ring‐closing metathesis (RCM) and one‐pot dichlorodicyanoquinone (DDQ) oxidation sequence to deliver 2‐substituted naphthalenes. In the second strategy, a double Claisen rearrangement and RCM protocol have been used as key steps to give highly functionalized benzoannulated quinone derivatives.     

Optimization of Ring‐Closing Metathesis: Inert Gas Sparging and Microwave Irradiation

A systematic study of a ring‐closing metathesis towards a tetrasubstituted double bond as part of a seven‐membered ring in a 5.7.5‐tricyclic guaianolide system is described. By combining two techniques, namely sparging an inert gas through the solution together with dielectric heating via microwave irradiation a high‐yielding ring‐closing metathesis reaction in this particularly challenging case was achieved. The results obtained compare favorably with conventional heating conditions or with microwave irradiation in a closed system. The key aspects seem to be that rapid microwave irradiation diminishes catalyst decay by allowing the required high reaction temperature to be reached quickly and homogeneously and thereby providing enough energy for a successful metathesis reaction, while inert gas sparging is purging off evolving ethylene to shift the equilibrium to the product.     

A Ring‐Closing Metathesis Approach to Cyclic α,β‐Dehydroamino Acids

A comprehensive study on the synthesis and ring‐closing metathesis (RCM) of α,β‐dehydroamino acids is described. This sequence has led to the formation of a range of biologically relevant functionalized nitrogen heterocycles. The incorporation of chiral building blocks in the RCM precursors eventually resulted in the formation of optically active 4‐substituted cyclic dehydroamino acids. In addition, olefin isomerization under metathesis conditions was observed for a number of compounds, which could be successfully inhibited either by the introduction of allylic substituents or by the addition of a ruthenium hydride scavenger.     

Unexpected Results of a Turnover Number (TON) Study Utilising Ruthenium‐Based Olefin Metathesis Catalysts

A turnover number (TON) study of ruthenium‐based metathesis catalysts has been conducted for ring‐closing metathesis (RCM) in dilute solution. Unexpectedly the results indicate that 1^st generation metathesis catalysts can give higher TON in RCM of simple unsubstituted terminal olefins than their second generation counterparts. In particular, the 1^st generation Hoveyda–Grubbs catalyst showed unexpectedly high activity, particularly when compared to the 2^nd generation catalysts.     

Non‐catalyst synthesis and in vitro drug release property of poly(5,5‐dimethyl‐1,3‐dioxan‐2‐one)‐block‐methoxy poly(ethylene glycol) copolymers

A series of poly(5,5‐dimethyl‐1,3‐dioxan‐2‐one)‐block‐methoxy poly(ethylene glycol) (PDTC‐b‐mPEG) copolymers were synthesized by the ring‐opening polymerization of 5,5‐dimethyl‐1,3‐dioxan‐2‐one (DTC) in bulk, using methoxy poly(ethylene glycol) (mPEG) as initiator without adding any catalysts. The resulting copolymers were characterized by Fourier transform infrared spectra, ¹H NMR and gel permeation chromatography. The influences of some factors such as the DTC/mPEG molar feed ratio, reaction time and reaction temperature on the copolymerization were investigated. The experimental results showed that mPEG could effectively initiate the ring‐opening polymerization of DTC in the absence of catalyst, and that the copolymerization conditions had a significant effect on the molecular weight of PDTC‐b‐mPEG copolymer. In vitro drug release study demonstrated that the amount of indomethacin released from PDTC‐b‐mPEG copolymer decreased with increase in the DTC content in the copolymer. © 2013 Society of Chemical Industry     

Relay Catalysis: Enantioselective Synthesis of Cyclic Benzo‐Fused Homoallylic Alcohols by Chiral Brønsted Acid‐Catalyzed Allylboration/Ring Closing Metathesis

Six‐ and seven‐membered benzo‐fused cyclic homoallylic alcohols can be readily synthesized by a tandem chiral Brønsted acid‐catalyzed allyl (crotyl)boration/ring closing metathesis sequence performed under orthogonal relay catalysis conditions. Excellent enantio‐ and diastereoselectivities are obtained in most of the cases. In addition, the parent crotylboration/RCM process is also described. The required substrates, ortho‐vinylbenzaldehydes, are readily available in one step from commercially available starting materials. Both catalysts and reactants are also available from commercial suppliers. The reaction shows broad functional group compatibility and is also suitable for heteroaromatic substrates. Substitution at any position of the aromatic ring is tolerated; however, substitution at position 6 results in a substantial drop in enantioselectivity.     

Synthesis and characterization of novel biodegradable poly(carbonate‐co‐phosphate)s

A series of aliphatic poly(carbonate‐co‐phosphate)s was synthesized in bulk using aluminium isopropoxide as initiator by ring‐opening polymerization with various cyclic carbonates (trimethylene carbonate (TMC) and 5,5‐dimethyltrimethylene carbonate (DTC)) and cyclic phosphates (ethylene ethyl phosphate (EEP), ethylene isobutyl phosphate (EIBP), ethylene lauryl phosphate (ELP) and ethylene stearyl phosphate (ESP)). The influence of reaction conditions such as polymerization time, polymerization temperature and initiator concentration on the yield and molecular weight were investigated. The substituent effect of the cyclic monomers on the polymerization was also studied, and the results indicate that the substituents exert a marked influence on the molecular weight of the copolymers obtained. The comonomer reactivity ratios were determined (TMC 0.88 and EEP 1.17). The copolymers with backbone chains rich in phosphate content exhibit better hydrophilicity than that of TMC homopolymer, and the degradation rate of the copolymers increases with the increase of phosphate content therein. © 2001 Society of Chemical Industry     

Biomimetic Formation of 2‐Tropolones by Dioxygenase‐Catalysed Ring Expansion of Substituted 2,4‐Cyclohexadienones

Substituted 2‐tropolone natural products are found in plants and fungi. Their biosynthesis is thought to occur by ring expansion from a cyclohexadienone precursor, but this reaction has not previously been demonstrated experimentally. Treatment of 6‐hydroxy‐6‐hydroxymethylcyclohexa‐2,4‐dienone with the non‐haem iron(II)‐dependent extradiol catechol dioxygenase MhpB from Escherichia coli results in the formation of the 2‐tropolone ring‐expansion product through a pinacol‐type rearrangement. Three further substituted cyclohexa‐2,4‐dienone analogues were prepared, and treatment of each analogue was found to give the substituted 2‐tropolone ring‐expansion product. This ring expansion could also be effected nonenzymatically by treatment with 1,4,7‐triazacyclononane and FeCl₂. This is a novel transformation for non‐haem iron‐dependent enzymes, and this is the first experimental demonstration of the proposed ring‐expansion reaction in tropolone biosynthesis.     

Synthesis of PLLA‐PEOMA comb‐block‐comb type molecular brushes based on AGET ATRP and ring‐opening polymerization

BACKGROUND: Molecular brushes are types of macromolecules with densely grafted side chains on a linear backbone. The synthesis of macromolecular brushes has stimulated much interest due to their great potential in applications in various fields. Poly(L ‐lactide)–poly(ethylene glycol) methyl ether methacrylate (PLLA‐PEOMA) comb‐block‐comb molecular brushes with controlled molecular weights and narrow molecular weight distributions were successfully synthesized based on a combination of activator generated by electron transfer (AGET) atom transfer radical polymerization (ATRP) and ring‐opening polymerization. The synthetic route is a combination of the ‘grafting through’ method for AGET ATRP of the PEOMA comb block and the ‘grafting from’ method for the synthesis of the PLLA comb block. Poly(2‐hydroxyethyl methacrylate) (PHEMA) was synthesized by ATRP, and PLLA side chains and PEOMA side chains were grown from the backbones and the terminal sites of PHEMA, respectively. RESULTS: The number‐average degrees of polymerization of PLLA chains and poly[poly(ethylene glycol) methyl ether methacrylate] (PPEOMA) comb blocks were determined using ¹H NMR spectroscopy, and the apparent molecular weights and molecular weight distributions of the brush molecules were measured using gel permeation chromatography. The crystallization of the components in the comb‐block‐comb copolymers was also investigated. The crystallization of PLLA side chains is influenced by PLLA chain length and the content of PPEOMA in the molecular brushes. The comb‐block‐comb copolymer composed of hydrophobic PLLA and hydrophilic PEOMA can self‐assemble into a micellar structure in aqueous solution. CONCLUSION: A combination of AGET ATRP and ring‐opening polymerization is an efficient method to prepare well‐defined comb‐block‐comb molecular brushes. The physical properties of the molecular brushes are closely related to their structures. Copyright © 2009 Society of Chemical Industry     

Polyethylene‐block‐poly(ε‐caprolactone) diblock copolymers: synthesis and compatibility

A strategy is introduced for the synthesis of polyethylene‐block‐poly(ε‐caprolactone) block copolymers by a combination of coordination polymerization and ring‐opening polymerization. First, end‐hydroxylated polyethylene (PE‐OH) was prepared with a one‐step process through ethylene/3‐buten‐1‐ol copolymerization catalyzed by a vanadium(III) complex bearing a bidentate [N,O] ligand ([PhN?C(CH₃)CHC(Ph)O]VCl₂(THF)₂). The PE‐OH was then used as macroinitiator for ring‐opening polymerization of ε‐caprolactone, leading to the desired nonpolar/polar diblock copolymers. The block structure was confirmed by spectral analysis using ¹H NMR, gel permeation chromatography and differential scanning calorimetry. The unusual topologies of the model copolymers will establish a fundamental understanding for structure–property correlations, e.g. compatibilization, of polymer blends and surface and interface modification of other polymers. © 2014 Society of Chemical Industry     

Influence of copolymerization conditions on the structure and properties of polyethylene/polypropylene/poly(ethylene‐co‐propylene) in‐reactor alloys synthesized in gas‐phase with spherical ziegler‐natta catalyst

A spherical TiCl₄/MgCl₂‐based catalyst was used in the synthesis of polyethylene/polypropylene/poly (ethylene‐co‐propylene) in‐reactor alloys by sequential homopolymerization of ethylene, homopolymerization of propylene, and copolymerization of ethylene and propylene in gas‐phase. Different conditions in the third stage, such as the pressure of ethylene–propylene mixture and the feed ratio of ethylene, were investigated, and their influences on the compositions, structural distribution and properties of the in‐reactor alloys were studied. Increasing the feed ratio of ethylene is favorable for forming random ethylene–propylene copolymer and segmented ethylene–propylene copolymer, however, slightly influences the formation of ethylene‐b‐propylene block copolymer and homopolyethylene. Raising the pressure of ethylene–propylene mixture results in the increment of segmented ethylene–propylene copolymer, ethylene‐b‐propylene block copolymer, and PE fractions, but exerts a slight influence on both the random copolymer and PP fractions. The impact strength of PE/PP/EPR in‐reactor alloys can be markedly improved by increasing the feed ratio of ethylene in the ethylene–propylene mixture or increasing the pressure of ethylene–propylene mixture. However, the flexural modulus decreases as the feed ratio of ethylene in the ethylene–propylene mixture or the pressure of ethylene–propylene mixture increases. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 2481–2487, 2006     

Ring‐opening polymerization of ε‐caprolactone by a new yttrium complex: Y[2,2′‐ethylidene‐bis(4,6‐di‐tert‐butylphenoxy)]2(ethylene glycol dimethyl ether)Na(ethylene glycol dimethyl ether)3

The main aims of the work reported here were to synthesize and characterize a new 2,2′‐ethylidene‐bis(4,6‐di‐tert‐butylphenol) (EDBPH₂)‐based bimetal yttrium complex, Y(EDBP)₂(DME)Na(DME)₃ (1c; where DME is ethylene glycol dimethyl ether), which was employed as an efficient initiator for the ring‐opening polymerization of ε‐caprolactone (ε‐CL). From single‐crystal X‐ray diffraction, the solid structure of this new bimetal initiator was well established. Experimental results show that 1c initiates the ring‐opening polymerization of ε‐CL to afford poly(ε‐CL) with a narrow molecular weight distribution (M_w/M_n = 1.09–1.36, 65 °C). Based on an in situ NMR study, a plausible coordination–insertion mechanism is then proposed. The bimetal complex 1c can be used as an initiator for the ring‐opening polymerization of ε‐CL with some living characteristics. A study of the mechanism reveals that DME displacement in 1c by ε‐CL is involved in the initiation process and the propagation may proceed through three pathways by Na? O insertion or Y? O insertion. Copyright © 2009 Society of Chemical Industry     

Stripe coating with a coffee‐ring effect for color filter solutions

The coffee‐ring effect of a coated narrow stripe approximately 350 μm wide was examined. The coating solution was based on a new formulation with a specific application for the production of color filters used in liquid‐crystal display panels. The basic components of this formulation were color pigments, solvents, and a novel alkali solution resin. The resin was a copolymer consisting of methacrylic acid, hydroxyl ethyl methacrylate, and methyl methacrylate. Three solvents with different boiling points were used: propylene glycol methyl ether acetate, methyl ethyl ketone, and tetrahydrofuran. The formation of a coffee ring on the coated stripe was mainly dependent on the solvent evaporation rate and the acid value of the copolymer. The acid value determined the strength of the hydrogen bonding of the copolymer. Fourier transform infrared analysis revealed that the intramolecular hydrogen bonding of the carbonyl groups of hydroxyl ethyl methacrylate was one of the critical factors affecting the formation of a coffee ring. The other factor was the rate of solvent evaporation. A proper adjustment of the acid value combined with a highly volatile solvent could effectively eliminate the formation of a coffee ring. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

pH‐responsive core crosslinked polycarbonate micelles via thiol‐acrylate Michael addition reaction

A facile method for the construction of pH‐responsive core crosslinked micelles (CCLMs) based on polycarbonate was developed. Biodegradable amphiphilic block copolymer monomethoxy poly(ethylene glycol)‐b‐Poly(AC) (mPEG‐b‐poly(AC)) with pendant acrylate group was synthesized by means of ring opening polymerization of acryloyl carbonate (AC). Then CCLMs were obtained via thiol‐acrylate Michael addition reaction between the pendant acrylate group in the hydrophobic block and the crosslinker 1,6‐hexanedithiol. DLS results showed that the CCLMs prepared from mPEG‐b‐poly(AC)₂₅ were more stable than uncrosslinked micelles (UCLMs) upon dilution by 10‐fold DMF. Model drug Coumarin 102 was then encapsulated into the micelles. The pH‐responsive release of coumarin 102 from the CCLMs was demonstrated by fluorescence spectroscopy. The core crosslinked polycarbonate micelles have a potential as efficient intracellular smart drug delivery platforms. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44421.     

The Stereoselective Ru3(CO)12‐Catalyzed Synthesis of Steroidal 1,3‐Dihydropyrrol‐2‐one Derivatives from α,β‐Unsaturated Imines,Carbon Monoxide and Ethylene

The reaction of α,β‐unsaturated imines, derived from steroidal amines and cinnamaldehyde, with carbon monoxide and ethylene leads to the formation of steroids with a 1,3‐dihydropyrrol‐2‐one ring system attached to the D‐ring of the steroid. In addition, a new stereogenic center at C‐3 of the pyrrolone ring is produced during the reaction sequence. In the case of a 16‐position of the imine moiety the yields are nearly quantitative but the diastereoselectivity is low whereas the sterically more hindered 17‐position shows a decreased reactivity but quite good diastereoselectivities. Complete diastereoselectivity is achieved if the starting compound exhibits an additional silyl ether group in the 17β‐position besides the imine subunit in the 16β‐position. The compound bearing the pyrrolone substituent at 17β‐position was characterized by means of X‐ray crystallography showing that the rotation of the pyrrolone ring is hindered by a strong intramolecular hydrogen bond between the carbonyl oxygen of the pyrrolone moiety and the hydrogen at C‐17. The question of whether this intramolecular hydrogen bond is also responsible for the observed diastereoselectivities is discussed.     

Fully degradable antibacterial poly(ester‐phosphoester)s by ring‐opening polymerization, “click” chemistry,and quaternization

Fully degradable cationic poly(ester‐phosphoester)s with antibacterial properties were prepared by a combination of ring‐opening polymerization (ROP) and “click” reaction. First, poly(ester‐phosphoester)s‐bearing alkynyl groups were synthesized by the ring‐opening copolymerization of 2‐(2‐propynyloxy)?2‐oxo‐1,3,2‐dioxaphospholane (propynyl ethylene phosphate, PEP) and ε‐caprolactone (CL) using lanthanum tris(2,6‐di‐tert‐butyl‐4‐methylphenolate)s (La(DBMP)₃) as the catalyst. 2‐Azido‐N,N‐dimethylethanamine (DMEAN₃) was then attached to the copolymers by “click” reaction, resulting in poly(ester‐phosphoester)s with pendant tertiary amines. After the quaternization reactions between the copolymer and various alkyl bromides, cationic poly(ester‐phosphoester)s containing ammonium groups were obtained. Optical density (OD) measurement shows that the cationic copolymers have excellent antibacterial activity, which makes them potential candidates as biomaterials. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42647.     

Ferrocene Redox Controlled Reversible Immobilization of Ruthenium Carbene in Ionic Liquid: A Versatile Catalyst for Ring‐Closing Metathesis

A ferrocene‐tagged ruthenium carbene 15 that can be reversibly immobilized in an ionic liquid (IL) via the controlled oxidation and reduction of a ferrocene tag was prepared. This offers a new strategy which uses redox chemistry to control immobilization and to recycle both the catalyst and the IL. In this experiment, 11 recycles were performed for the ring‐closing metathesis (RCM) of a substrate using 16 as the catalyst in an ionic liquid (IL). More importantly, after the reaction was completed, the ruthenium catalyst was easily separated from the supporting IL by just adding decamethylferrocene (DMFc) to reduce the cationic ferrocene and then extracting it with benzene. Thus, this recycle system offers an easy way to recycle both the ruthenium catalyst and the IL.