Dissertation committee:
Γεώργιος Χ. Βουγιουκαλάκης, Αναπληρωτής Καθηγητής, Τμήμα Χημείας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Δημήτριος Γεωργιάδης, Καθηγητής, Τμήμα Χημείας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Αθανάσιος Γκιμήσης, Καθηγητής, Τμήμα Χημείας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Αντώνης Κολοκούρης, Καθηγητής, Τμήμα Φαρμακευτικής Χημείας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Μανώλης Στρατάκης, Καθηγητής, Τμήμα Χημείας, Πανεπιστήμιο Κρήτης
Κωνσταντίνος Νεοχωρίτης, Επίκουρος Καθηγητής, Τμήμα Χημείας, Πανεπιστήμιο Κρήτης
Γιώργος Ρώτας, Επίκουρος Καθηγητής, Τμήμα Χημείας, Πανεπιστήμιο Ιωαννίνων
Summary:
Multicomponent reactions have become a fascinating tool to construct complex molecules with great elegance, given that the intermediates involved in these processes are not isolated, thus providing easy access to organic compounds with relatively low synthetic effort. In this thesis, several aspects of multicomponent reactions are studied, towards synthetically valuable compounds.
In chapter 1, an introduction to the aspects that will be discussed in the following chapters of this thesis are provided. The applications of multicomponent reactions are initially briefly presented, through the discussion of some examples. Mainly three cases are discussed: propargylamines, allenes, and thiazolidin-2-imines. Next, a brief overview of heterocycles construction, by exploiting ο-hydroxyphenyl propargylamines and 4-hydroxycoumarins is given. Finally, an introduction to fullerenes and their applications is provided, followed by the application of N-heterocyclic carbene-coordinated iridium complexes in transfer hydrogenation reactions.
In chapter 2, the synthesis of trisubstituted allenes via a one-pot, three component reaction by reacting amines, ketones and alkynes is presented. Specifically, a new protocol for the synthesis of synthetically challenging trisubstituted allenes is reported, by using only one catalyst and with lower catalyst loading, when compared to the preexisting protocols. Optimization experiments are presented in detail, followed by the evaluation of a series of substrates. Structurally and synthetically interesting compounds are among others synthesized, showcasing the catalytic potential of the developed protocol. Finally, mechanistic experiments, involving control experiments, deuterium labeling experiments, kinetic isotope measurements, as well as DFT calculations, are presented, towards elucidating the mechanism of the reaction.
In chapter 3, the synthesis of thiazolidin-2-imines via a one-pot, four-component reaction employing amines, ketones, alkynes and isothiocyanates is presented. The reaction is catalyzed by an inexpensive copper catalyst, under very low catalyst loadings. In this regard, ketones are introduced in this multicomponent reaction for the first time. Optimization experiments are first presented, followed by a thorough study of a variety of ketones, amines, alkynes, and isothiocyanates. Control experiments along with theoretical calculations provided information which directed us in proposing a reaction mechanism.
Chapter 4 is split into two sections: The first involves preliminary results on the reactivity of o-hydroxyphenyl propargylamines with 4-hydroxycoumarins, where the difficulties encountered are discussed. Although some positive results were obtained, the same transformation was reported by another group during the course of our work, which prompted us to stop working on this project. The second part involves preliminary results on the design of a protocol for the construction of heterocycles through a multicomponent reaction, followed by an Ullmann coupling. Each step is studied separately, and all major issues are addressed.
In chapter 5, the synthetic endeavors towards C60-porphyrin and a C60-terpyridine dyads by exploiting the A3 coupling reaction are presented. A strategy for the synthesis of a C60-propargylamine derivative is initially presented, followed by the unsuccessful attempts to construct C60-porphyrin and C60-terpyridine dyads, by exploiting this strategy.
In chapter 6, the study of a family of four iridium-NHC complexes is described, for their capacity to reduce prochiral ketones to optically pure tertiary alcohols, via the transfer hydrogenation strategy. In this regard, optimization experiments are discussed, followed by the study of several prochiral ketones. In addition, the synthetic efforts towards two families of platinum and palladium NHC coordinated complexes are addressed.
Keywords:
Catalysis, multicomponent reactions, A3 reaction, K2 reaction, allenes, propargylamines, thiazolidin-2-imines, 4-hydroxycoumarins, fullerenes, N-heterocyclic carbenes, asymmetric transfer hydrogenation
