Mechanistic studies of the Cu-catalyzed C-N coupling of sterically hindered aryl iodides with sterically hindered anilines are carried out to shed light on how a recently reported pyrrol-ol ligand affects the reaction. Kinetic, spectroscopic, and computational tools help to probe the nature of the active catalyst species and the rate-determining step in the cycle. In contrast to most known Cu systems, oxidative addition is found to precede coordination of the amine. These studies help to design an efficient process under mild conditions using a fully homogeneous system as well as protocols that enable high yields by temperature scanning and controlled addition of the base. The insights obtained for the XX-type ligand may lead to a general approach for challenging substrate classes in Cu-catalyzed coupling reactions.

We describe the synthesis of Fe(ii)-based octahedral coordination cages supported by calixarene capping ligands. The most porous of these molecular cages has an argon accessible BET surface area of 898 m(2) g(-1) (1497 m(2) g(-1) Langmuir). The modular synthesis of molecular cages allows for straightforward substitution of both the bridging carboxylic acid ligands and the calixarene caps to tune material properties. In this context, the adsorption enthalpies of C-2/C-3 hydrocarbons ranged from -24 to -46 kJ mol(-1) at low coverage, where facile structural modifications substantially influence hydrocarbon uptakes. These materials exhibit remarkable stability toward oxidation or decomposition in the presence of air and moisture, but application of a suitable chemical oxidant generates oxidized cages over a controlled range of redox states. This provides an additional handle for tuning the porosity and stability of the Fe cages.

An unsaturated polymer's cis/trans-olefin content has a significant influence on its properties. For polymers obtained by ring-opening metathesis polymerization (ROMP), the cis/trans-olefin content can be tuned by using specific catalysts. However, cis-selective ROMP has suffered from narrow monomer scope and lack of control over the polymerization (giving polymers with broad molecular weight distributions and prohibiting the synthesis of block copolymers). Herein, we report the versatile cis-selective controlled living ROMP of various endo-tricyclo[4.2.2.02,5]deca-3,9-diene and various norbornene derivatives using a fast-initiating dithiolate-chelated Ru catalyst. Polymers with cis-olefin content as high as 99% could be obtained with high molecular weight (up to Mn of 105.1 kDa) and narrow dispersity (<1.4). The living nature of the polymerization was also exploited to prepare block copolymers with high cis-olefin content for the first time. Furthermore, owing to the successful control over the stereochemistry and narrow dispersity, we could compare cis- and trans-rich polynorbornene and found the former to have enhanced resistance to shear degradation.

The synthesis of E-macrocycles is achieved using stereoretentive, Ru-based olefin metathesis catalysts supported by dithiolate ligands. Kinetic studies elucidate marked differences in activity among the catalysts tested, with catalyst 4 providing meaningful yields of products in much shorter reaction times than stereoretentive catalysts 2 and 3. Macrocycles were generated with excellent selectivity (>99% E) and in moderate to high yields (47–80% yield) from diene starting materials bearing two E-configured olefins. A variety of rings were constructed, ranging from 12to 18-membered macrocycles, including the antibiotic recifeiolide.

Since the advent of olefin metathesis, stereoselective olefin metathesis catalysts have been sought after for use in academic and industrial applications. The most recently reported Ru-complex for Z-selective olefin metathesis features a catechothiolate ligand, and this catalyst has been shown to be esp. useful in ring-opening metathesis polymn. and ringopening-cross metathesis. However, this catalyst is prone to deactivation, as the electron-rich sulfur in the catechodithiolate ligand is susceptible to undergo a 1,2-shift to the neighboring electrophilic alkylidene, which effectively deactivates the catalyst. Hoveyda et al. used electroneg. groups on the dithiolate ligand to diminish the rate of the proposed isomerization and thus favor olefin metathesis towards high-value Z-allylic alc. products. However, a deeper study of the mechanism of deactivation and a further anal. of the electronic structure is necessary in order to understand the deactivation pathway and tune the catalyst to disfavor this 1,2-shift. Guided by expts., we present a computational study of the reaction pathway and present results on the electronic nature of the catalytically active species. We study the propensity for the catalytic species to undergo deactivation by analyzing the altered electronic structure that results from substrate coordination and alkylidene substitution. This work serves as grounds for understanding the reactivity of this new class of Ru-complexes and we propose design principles for further development of these catalysts for academic and industrial use.

The addition of vinyl ethers to Z-selective, cyclometalated ruthenium metathesis catalysts generates Fischer carbene complexes. Although Fischer carbenes are usually thought to be metathesis inactive, we show that Fischer carbenes are metathesis active under certain circumstances. These species were found to decompose facilely to Ru hydride complexes, as identified by both experiment and computation. Since vinyl ethers are often used to quench metathesis reactions implementing Ru-based metathesis catalysts, their decomposition to hydrides can have a deleterious effect on the desired stereochemistry of the olefin product.

Transition metal-catalyzed olefin metathesis has emerged as a powerful tool for constructing C−C double bonds. This thesis delineates the development of Ru-based catalysts for the stereoselective formation of olefins and mechanistic studies used to examine how catalyst structure influences selectivity and activity. Chapter 2 details the synthesis of Z-selective, cyclometalated catalysts bearing nitrite X-ligands. The activity and selectivity of these catalysts were examined in an array of ring-opening metathesis polymerization and cross metathesis reactions. Comparison of these catalysts with their nitrate-bound analogues is described. Chapter 3 describes the examination of several Z-selective, cyclometalated catalysts in ring-opening metathesis polymerizations. The polymerizations of a variety of norbornene and norbornene derivatives were examined to determine the tacticity and microstructure of the resulting polymer. Computational studies were used to examine the mechanism of the polymerization reactions. Chapter 4 examines the decomposition of Fischer carbene complexes derived from cyclometalated catalysts. In-depth NMR studies are used to determine the identity of the decomposition product, and the decomposition pathway is examined through computational studies. Chapter 5 describes the first example of highly E-selective cross metathesis through kinetic control using stereoretentive, Ru-based catalysts bearing dithiolate catalysts. The preparation of additional stereoretentive catalysts is described for increasing catalyst activity while maintaining or increasing selectivity. A model for the observed stereoselectivity is proposed. Chapter 6 delineates the preparation of a series of fast initiating, stereoretentive catalysts. These catalysts are assessed in an array of cross metathesis reactions, and significantly enhanced activity is observed in E-selective reactions. The examination of the relationships between the structure of a catalyst and its selectivity and activity is described. Chapter 7 examines the use of stereoretentive catalysts in the synthesis of Z-macrocycles from diene starting materials bearing a Z-olefin and a terminal olefin. Initiation rate studies are conducted to examine the activity of these catalysts compared to previously reported cyclometallated catalysts used in this ring-closing metathesis reaction. The synthesis of twelve- to seventeen-membered rings with high Z-selectivity is described. Chapter 8 explores the use of fast-initiating, stereoretentive catalysts for synthesizing E-macrocycles. The preparation of diene starting materials containing two E-olefins is described. Using these catalysts, twelve- to eighteen-membered rings are constructed with high E-selectivity.

Delta(12)-Prostaglandin J family is recently discovered and has potent anticancer activity. Concise syntheses of four Delta(12)-prostaglandin J natural products (7-8 steps in the longest linear sequences) are reported, enabled by convergent stereoretentive cross-metathesis. Exceptional control of alkene geometry was achieved through stereoretention.

The synthesis of E-macrocycles is achieved using stereoretentive, Ru-based olefin metathesis catalysts supported by dithiolate ligands. Kinetic studies elucidate marked differences in activity among the catalysts tested, with catalyst 4 providing meaningful yields of products in much shorter reaction times than stereoretentive catalysts 2 and 3. Macrocycles were generated with excellent selectivity (>99% E) and in moderate to high yields (47-80% yield) from diene starting materials bearing two E-configured olefins. A variety of rings were constructed, ranging from 12- to 18-membered macrocycles, including the antibiotic recifeiolide.

Ru-based metathesis catalysts employed in cyclopolymerization (CP) of 1,6-heptadiyne derivatives have promoted regioselective α-addition to alkynes, forming various conjugated polyenes containing exclusively five-membered repeat units. Recently, we discovered that a new chelated Ru catalyst could promote regioselective β-addition to produce analogous polyenes containing six-membered rings with moderate to good β-selectivity. Since then, we have focused our research on pursuing more active and β-selective regiocontrol to produce conjugated polymers with excellent β-selectivity, with a much broader range of monomers. Herein, we demonstrate highly β-selective CP by combining a new dithiolate-chelated Ru-based catalyst with weakly coordinating pyridine additives, which significantly enhance the conversion and β-selectivity. An in-depth mechanistic investigation by ^1H NMR revealed a prominent role for the additives, which improve the stability of the propagating carbene.

A highly efficient, Z-selective ring-closing metathesis system for the formation of macrocycles using a stereoretentive, ruthenium-based catalyst supported by a dithiolate ligand is reported. The catalyst is remarkably active as observed in initiation experiments showing complete catalyst initiation at -20 °C within 10 minutes. Macrocyclization reactions generated Z-products from easily accessible diene starting materials bearing a Z-olefin moiety. This approach provides a more efficient and selective route to Z-macrocycles relative to previously reported systems. Reactions were completed within shorter reaction times, and turnover numbers of up to 100 could be achieved. Macrocyclic lactones ranging in size from twelve- to seventeen-membered rings were synthesized in moderate to high yields (67-79 %) with excellent Z-selectivity (95-99 %).

Olefin metathesis is an incredibly valuable transformation that has gained widespread use in both academic and industrial settings. Lately, stereoretentive olefin metathesis has garnered much attention as a method for the selective generation of both E- and Z-olefins. Early studies employing ill-defined catalysts showed evidence for retention of the stereochemistry of the starting olefins at low conversion. However, thermodynamic ratios E/Z were reached as the reaction proceeded to equilibrium. Recent studies in olefin metathesis have focused on the synthesis of catalysts that can overcome the inherent thermodynamic preference of an olefin, providing synthetically useful quantities of a kinetically favored olefin isomer. These reports have led to the development of stereoretentive catalysts that not only generate Z-olefins selectively, but also kinetically produce E-olefins, a previously unmet challenge in olefin metathesis. Advancements in stereoretentive olefin metathesis using tungsten, ruthenium, and molybdenum catalysts are presented.

AbstractDie Olefinmetathese ist ein wertvolles Verfahren für Wissenschaft und Industrie. In letzter Zeit rückte die stereoretentive Olefinmetathese als eine Methode für die selektive Erzeugung von sowohl E‐ als auch Z‐Olefinen in den Fokus. In früheren Untersuchungen wurde nachgewiesen, dass die stereochemische Konfiguration der Ausgangsolefine zu Anfang der Umwandlung beibehalten wird. Als sich die Reaktion dem Gleichgewichtszustand näherte, wurden jedoch thermodynamische E/Z‐Verhältnisse erreicht. Bei neueren Untersuchungen lag das Hauptaugenmerk auf der Synthese von Katalysatoren, mit denen die inhärente thermodynamische Präferenz eines Olefins überwunden und ein kinetisch begünstigtes Olefinisomer erzeugt werden kann. Diese Berichte führten zur Entwicklung von stereoretentiven Katalysatoren, mit denen nicht nur selektiv Z‐Olefine erhalten werden, sondern auch E‐Olefine. Fortschritte bei der stereoretentiven Olefinmetathese unter Verwendung von Wolfram‐, Ruthenium‐ und Molybdänkatalysatoren werden hier dargelegt.

Ruthenium-based olefin metathesis catalysts bearing dithiolate ligands have been recently employed to generate olefins with high E-selectivity (>99% E) but have been limited by low to moderate yields. In this report, 1H NMR studies reveal that a major contributing factor to this low activity is the extremely low initiation rates of these catalysts with trans olefins. Introducing a 2-isopropoxy-3-phenylbenzylidene ligand in place of the conventional 2-isopropoxybenzylidene ligand resulted in catalysts that initiate rapidly under reaction conditions. As a result, reactions were completed in significantly less time and delivered higher yields than those in previous reports while maintaining high stereoselectivity (>99% E).

The microstructures of polymers produced by ring-opening metathesis polymerization (ROMP) with cyclometalated Ru-carbene metathesis catalysts were investigated. A strong bias for a cis,syndiotactic microstructure with minimal head-to-tail bias was observed. In instances where trans errors were introduced, it was determined that these regions were also syndiotactic. Furthermore, hypothetical reaction intermediates and transition structures were analyzed computationally. Combined experimental and computational data support a reaction mechanism in which cis,syndio-selectivity is a result of stereogenic metal control, while microstructural errors are predominantly due to alkylidene isomerization via rotation about the Ru═C double bond.

The first kinetically controlled, highly trans-selective (>98%) olefin cross-metathesis reaction is demonstrated using Ru-based catalysts. Reactions with either trans or cis olefins afford products with highly trans or cis stereochemistry, respectively. This E-selective olefin cross-metathesis is shown to occur between two trans olefins and between a trans olefin and a terminal olefin. Additionally, new stereoretentive catalysts have been synthesized for improved reactivity.

A series of ruthenium metathesis catalysts contg. a cyclometalated N- heterocyclic carbene (NHC) ligand were examd. in the ring opening metathesis polymn. (ROMP) of norbornene- and norbornadiene- derived monomers. In general, the resulting polymers were found to be highly cis with syndiotactic- biased cis and trans regions, while blockiness calcns. showed that trans double bonds occurred randomly throughout the polymers. These structural trends suggest that the controlling factor in cis selectivity and tacticity is the combined influence of the stereogenic ruthenium center and the steric environment surrounding the alkylidene on monomer approach. These conclusions are further supported by preliminary computational studies, which are ongoing and will also be discussed. It is expected that these results will provide invaluable insight into the mechanism and mode- of- action of cyclometalated ruthenium metathesis catalysts and will be instrumental in the design of future catalysts for cis- selective metathesis transformations.

The Z-content of products generated in reactions catalyzed by adamantyl-activated Z-selective metathesis catalysts is at first very high but degrades at higher conversions. The degree to which this undesirable process occurs is dependent on both the substrate and catalyst structure. Studies of Z-to-E isomerization processes and methods of preventing them are explored. Furthermore, an interesting Fischer carbene species was found to affect these isomerization processes.