Types and properties of metal-free catalysts for living polymerizations of biomaterials

Syntéza biokompatibilních a biodegradabilních polyesterů, použitelných převážně v medicíně, využívá pro polymeraci za otevření kruhu katalyzátory na bázi kovu (např. Sn, Al atd.), které se mohou po implantaci deponovat v těle. Podstatou bakalářské práce je popis netoxických "metal-free" karbenových sloučenin a jejich vlastností použitelných jako katalyzátory pro polymeraci cyklických esterů. Příprava těchto stabilních karbenových katalyzátorů a jejich charakterizace je cílem experimentání práce.Synthesis of biocompatible and biodegradable polyesters applicable mainly in biomedicine uses metal catalysts (based on Sn, Al etc.) for ring opening polymerization, which could be deposited in a body after implantation. Objective of the bachelor thesis is description of non-toxic metal-free carbene compounds and their properties utilizable as catalysts for polymerization of cyclic esters. Preparation of these stable free carbene catalysts and their characterization is the main goal of the experimental work.

Reactive Palladium Carbenes: Migratory Insertion and Other Carbene-Hydrocarbyl Coupling Reactions on Well-Defined Systems

Producción CientíficaPalladium complexes with carbene ligands are among the best known and more extensively used catalysts. Those carbenes are usually NHC or N,N-disubstituted derivatives and their use relies on the robust nature of the carbene ligands and their role as auxiliary ligands that modify the metal's elec- tronic and steric features. In contrast, there are other types of carbenes that, when coordinated to palladium, lead to transfor- mations in which the carbene fragment is involved. In the last decade, palladium-catalyzed reactions have been extended to the use of carbene precursors that can be functionalized with the formation of several C–C bonds in one reaction step. Plausi- ble mechanisms have been proposed where a carbene–hydro- carbyl coupling occurs in the palladium coordination sphere. This microreview aims to collect and discuss the examples of organometallic reactions in well-characterized palladium com- plexes where the carbene is one of the fragments involved in C–C bond formation. These examples are key in understanding and supporting the mechanisms proposed for the Pd-catalyzed of C–C coupling reactions of carbenes.MINECO (SGPI, grant CTQ2016-80913-P)Junta de Castilla y León (grants VA062G18 and VA051P17

Factors Dictating Carbene Formation at (PNP)Ir

The mechanistic subtleties involved with the interaction of an amido/bis(phosphine)-supported (PNP)Ir fragment with a series of linear and cyclic ethers have been investigated using density functional theory. Our analysis has revealed the factors dictating reaction direction toward either an iridium-supported carbene or a vinyl ether adduct. The (PNP)Ir structure will allow carbene formation only from accessible carbons α to the ethereal oxygen, such that d electron back-donation from the metal to the carbene ligand is possible. Should these conditions be unavailable, the main competing pathway to form vinyl ether can occur, but only if the (PNP)Ir framework does not sterically interfere with the reacting ether. In situations where steric hindrance prevents unimpeded access to both pathways, the reaction may progress to the initial C−H activation but no further. Our mechanistic analysis is density functional independent and whenever possible confirmed experimentally by trapping intermediate species experimentally. We have also highlighted an interesting systematic error present in the DFT analysis of reactions where steric environment alters considerably within a reaction

Novel "green" catalysts for controlled ring-opening polymerization of lactide

Syntéza polylaktidu (PLA) polymerací za otevření kruhu cyklického monomeru (ROP) může být uskutečněna různými způsoby. Literatura uvádí více než 100 katalytických systémů, jejichž pomocí lze polylaktid a jiné biodegradabilní alifatické polyestery získat. Například organokovové katalyzátory na bázi Sn, Zn, Al atd. se po splnění své polymerační funkce stávají kontaminanty a pro humánní implantáty je použití takového materiálu diskutabilní. V současné době jsou v centru výzkumné pozornosti nové N-heterocyklické karbenové katalyzátory. Tyto „metal-free“ katalytické struktury jsou schopné reprodukovatelně řídit syntézu polymerů předem definované molekulové hmotnosti s definovanými koncovými skupinami a nízkou polydisperzitou, která je charakteristická pro živý průběh polymerace. Nabízí se možnost syntézy blokových kopolymerů a různorodých makromolekulárních architektur. Předložená diplomová práce se zabývá studiem polymerace cyklického monomeru D,L-laktidu katalyzované N-heterocyklickým karbenem. Polymerace byly vedeny v přítomnosti benzylalkoholu jako iniciátoru v roztoku THF. Byl sledován vliv složení reakčního systému monomer – iniciátor – katalyzátor. Dále byly připraveny polymery opticky čistého L-laktidu s makroiniciátory PEG s Mn = 1000 a 2000 g/mol. Střední číselná molekulová hmotnost (Mn) a polydisperzita (PDI) byly stanoveny pomocí GPC. Definovatelnost koncových skupin vybraných polymerů byla prokázána pomocí 1H NMR.The synthesis of polylactide (PLA) by ring-opening polymerization (ROP) of cyclic monomer can be realized by different routes. More than 100 catalysts for the synthesis of polylactide and other biodegradable aliphatic polyesters are published in the literature. For example organometallic catalysts based on Sn, Zn, Al etc. after finishing polymerization function became contaminants and using obtained polymer material in human body is controversial. At present, the research is focused on novel N-hererocyclic carbene catalysts. These metal-free catalysts are able to produce polymers with controlled molecular weight, narrow polydispersity, end-group fidelity with high reproducibility as well as to synthesize the block copolymers and complex macromolecular architectures, which is characteristic for living polymerization system. This diploma thesis is focused on study of polymerization of cyclic monomer D,L-lactide catalyzed by N-hererocyclic carbene. Polymerizations were carried out at the presence of benzylalcohol as initiator at THF. We were focused on the influence of composition of reaction system monomer – initiator – catalyst. Polymers of optically pure L-lactide with macroinitiators PEG with Mn of 1000 a 2000 g/mol were prepared as well. Number average molecular weight (Mn) and polydispersity index (PDI) was determined by GPC. 1H NMR was used to prove end-group fidelity.

Probing the C-H Activation of Linear and Cyclic Ethers at (PNP)Ir

Interaction of the amido/bis(phosphine)-supported (PNP)Ir fragment with a series of linear and cyclic ethers is shown to afford, depending on substrate, products of α,α-dehydrogenation (carbenes), α,β-dehydrogenation (vinyl ethers), or decarbonylation. While carbenes are exclusively obtained from tert-amyl methyl ether, sec-butyl methyl ether (SBME), n-butyl methyl ether (NBME), and tetrahydrofuran (THF), vinyl ethers or their adducts are observed upon reaction with diethyl ether and 1,4-dioxane. Decarbonylation occurs upon interaction of (PNP)Ir with benzyl methyl ether, and a mechanism is proposed for this unusual transformation, which occurs via a series of C−H, C−O, and C−C bond cleavage events. The intermediates characterized for several of these reactions as well as the α,α-dehydrogenation of tert-butyl methyl ether (MTBE) are used to outline a reaction pathway for the generation of PNP-supported iridium(I) carbene complexes, and it is shown that the long-lived, observable intermediates are substrate-dependent and differ for the related cases of MTBE and THF. Taken together, these findings highlight the variety of pathways utilized by the electron-rich, unsaturated (PNP)Ir fragment to stabilize itself by transferring electron density to ethereal substrates through oxidative addition and/or the formation of π-acidic ligands

The development and use of novel iridium complexes as catalysts for ortho-directed hydrogen isotope exchange reactions

The preparation and application of groups of new iridium complexes are described. In particular, iridium complexes possessing phosphine ligands and a bulky N-heterocyclic carbene have been shown to be robust and readily handled species and have been applied in a range of directed hydrogen-deuterium and -tritium exchange processes and, in particular, with drug-like substrates or within ADMET-related studies. Overall, these new iridium(I) complexes are shown to be highly active catalysts and display catalytic activity far in excess of the industry standard, Crabtree's catalyst, with excellent levels of labelling being achieved over short reaction times and at low metal complex loadings, whilst tolerating a wide range of functional moieties. Furthermore and again in contrast to systems employing Crabtree's catalyst, the low catalyst loadings and short reaction times made possible by these emerging iridium carbene comple have delivered tritiated products with very good levels of labelling and without any appreciable by-product waste production