Deryn E. Fogg

Equilibrium Ring-Closing Metathesis

Ring-closing metathesis (RCM) of dienes is one of the most important methodologies now in use for the assembly of cyclic organic compounds. First employed by Villemin and by Tsuji nearly three decades ago,1,2 the reaction has risen to astonishing prominence in organic synthesis over the past decade, owing largely to the development of easily handled catalysts that enable controlled reaction.3 RCM represents a key step in many synthetic sequences: recent reviews describe its use in, inter alia, construction of synthetically valuable building blocks such as heterocyclic rings containing phosphorus,4 sulfur,4 oxygen,5 or nitrogen,5,6 including aromatic heterocycles;7 spirocyclic,8,9 cyclophane,8 and polycyclic compounds;8,9 and compounds of biological and medicinal relevance such as peptidomimetics,10,11 carbohydrate derivatives,11-14 alkaloids,11,15-19 bioactive cyclic molecules,20,21 and polycyclic ethers,22 including macrocyclic aza-crown ethers23 and topologically interesting molecules and “molecular machines”.24,25 While the common rings of 5-7 members have historically been dominant, owing in part to their greater ease of access, important advances have been made in the synthesis of medium20,26-30 and macrocyclic16,17,23,27,31-35 targets. One aspect of this review will examine the increased tendency of many medium and large rings to participate in equilibrium metathesis, and the resulting implications for selectivity and yields.

COMPOSITE THIN FILMS OF CDSE NANOCRYSTALS AND A SURFACE PASSIVATING/ ELECTRON TRANSPORTING BLOCK COPOLYMER : CORRELATIONS BETWEEN FILM MICROSTRUCTURE BY TRANSMISSION ELECTRON MICROSCOPY AND ELECTROLUMINESCENCE

We present a microscopic characterization of composite thin films made of CdSe semiconductor nanocrystals (quantum dots) dispersed in a polynorbornene-based block copolymer with surface-passivating and electron transport functionalities. We used two types of nanocrystals, CdSe with pure organic capping groups (“bare”) and CdSe–ZnS core-shell nanocrystals, also capped on the outer surface with organic groups. The composite thin films are incorporated in heterostructure light emitting devices where they serve as both the electron transport layer and the emissive layer. A thin layer of self-assembled poly (phenylene vinylene) (PPV) is used as the hole transport layer. We used transmission electron microscopy (TEM) to examine the film structure in plan view and in cross section. The TEM analysis uncovered distinct and complex differences between the microstructures of thin films containing bare and ZnS overcoated nanocrystals. We found a strong correlation between the composite film microstructure and the cor...

Olefin Metathesis at the Dawn of Implementation in Pharmaceutical and Specialty-Chemicals Manufacturing.

The recent uptake of molecular metathesis catalysts in specialty-chemicals and pharmaceutical manufacturing is reviewed.

Chemical Plants: High-Value Molecules from Essential Oils

As society faces a future of dwindling petrochemical supplies at increasing cost, much attention has been focused on methods to degrade biomass into renewable commodity-chemical building blocks. Reported here is a powerful complementary approach that amplifies the complexity of molecular structures present in plant materials. Essential-oil phenylpropenoids are transformed via acrylate cross-metathesis into potent antioxidants that are widely used in perfumery and cosmetics, and in treating disorders associated with oxidative damage.

A comparison of catalytic activity for imine hydrogenation using Ru ditertiary phosphine complexes, including chiral systems

Abstract A family of ruthenium ditertiary phosphine complexes was investigated for catalytic activity toward imine hydrogenation. The diphosphines (PP) used include chiral (chiraphos, diop, binap) and achiral (dppe, dppb) systems (chiraphos=Ph2PCH(Me)CH(Me)PPh2; diop=Ph2PCH2{ CHOCMe 2 O C}HCH2PPh2; binap=2,2′- bis(diphenylphosphino)-1,1′-binaphthyl; Ph2P(CH2),:PPh2 (n=2, dppe; n=4, dppb)). Activity was observed in MeOH at low catalyst concentrations (0.77 mM Ru), under moderate conditions (room temperature (r.t.), 1000 psi H2). The air-stable Ru2Cl5(PP)2 complexes were more active than the commonly used dimeric Ru2(II,II) systems to which they give rise in situ. Asymmetric induction in the prochiral ketimine PhCH2NC(Me)Ph was consistent, though modest, within the diop and binap series of neutral complexes, implying a common catalytic intermediate within each series. A maximum e.e. of 27% was found using Ru2Cl5(chiraphos)2 as catalyst; this represents a non-optimized figure for asymmetric induction, as no other prochiral ketimines were screened.

Isomerization During Olefin Metathesis: An Assessment of Potential Catalyst Culprits

Two ruthenium hydride complexes commonly proposed as agents of unintended isomerization during olefin metathesis are examined for their activity in isomerization of estragole, a representative allylbenzene. Neither proves kinetically competent to account for the levels of isomerization observed during cross‐metathesis of estragole by the second‐generation Grubbs catalyst. A structure–activity analysis of selected ruthenium hydride complexes indicates that higher isomerization activity correlates with a more electrophilic metal center.

Synthetic neoglycopolymer-recombinant human collagen hybrids as biomimetic crosslinking agents in corneal tissue engineering

Saturated neoglycopolymers, prepared via tandem ROMP-hydrogenation (ROMP=ring-opening metathesis polymerization) of carbohydrate-functionalized norbornenes, are investigated as novel collagen crosslinking agents in corneal tissue engineering. The neoglycopolymers were incorporated into recombinant human collagen type III (RHC III) as collagen crosslinking agents and glycosaminoglycan (GAG) mimics. The purely synthetic nature of these composites is designed to reduce susceptibility to immunological and allergic reactions, and to circumvent the transmission of animal infectious diseases. The collagen-neoglycopolymer biomaterials exhibit higher stability to collagenase-induced biodegradation than the control materials, composites of RHC III crosslinked using EDC/NHS (EDC=1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide; NHS=N-hydroxysuccinimide). Even at this proof of concept stage, the thermal stability, enzymatic resistance, and permeability of the neoglycopolymer hydrogels are comparable or superior to those of these fully optimized control materials, which have successfully been tested clinically. Tensile strength is adequate for transplantation, but lower than that of the optimized control materials.

Ethylene-Promoted versus Ethylene-Free Enyne Metathesis

The role of ethylene in promoting metathesis of acetylenic enynes is probed within the context of ring-closing enyne metathesis, using first- and second-generation Grubbs catalysts. Under inert atmosphere, rapid catalyst deactivation is observed by calibrated GC-FID analysis for substrates with minimal propargylic bulk. MALDI-TOF mass spectra reveal a Ru(enyne)(2) derivative that exhibits very low reactivity toward both enyne and ethylene. Under ethylene, formation of this species is suppressed. Enynes with bulky propargylic groups are not susceptible to this catalyst deactivation pathway, even under N(2) atmosphere.

Ligand manipulation and design for ruthenium metathesis and tandem metathesis-hydrogenation catalysis

Results of investigations into tandem ring-opening metathesis polymerization (ROMP)-hydrogenation are reviewed, in which hydrogen and 3-chloro-3-methyl-1-butyne provide simple chemical toggles to switch between metathesis and hydrogenation chemistry, enabling multiple tandem catalysis in chlorocarbon solvent. In the presence of methanol, hydrogenation of metathesis polymers can be carried out under 1 atm H 2 . Issues of ligand design are examined in developing new Ru-diphosphine catalysts with improved selectivity, and an important decomposition pathway is identified for RuCl 2 (PP)(CHR) systems (PP = chelating diphosphine).

Amine‐Mediated Degradation in Olefin Metathesis Reactions that Employ the Second‐Generation Grubbs Catalyst

Amine‐mediated decomposition during olefin metathesis reactions that employ the second‐generation Grubbs catalyst is studied. For most amines, the dominant deactivation pathway involves ejection of the PCy3 (Cy=cyclohexyl) ligand by the amine, followed by abstraction of the methylidene moiety from the resting‐state species RuCl2(H2IMes)(PCy3)(=CH2) (H2IMes=1,3‐dimesityl‐4,5‐dihydroimidazol‐2‐ylidene) as [MePCy3]Cl. An exception is highly basic 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU), which is slow to degrade the resting‐state methylidene complex, and for which the phosphonium byproduct is not observed. However, DBU is shown to rapidly attack a species generated during catalysis, most probably the metallacyclobutane intermediate.