Unit:
Department of PharmacyLibrary of the School of Science
Author:
Stylianakis Ioannis
Dissertation committee:
Αντώνιος Κολοκούρης, Καθηγητής, Τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Aθηνών
Carlos Silva Lopez, Καθηγητής, Faculty of Chemistry, University of Vigo, Spain
Ανδρέας Τσοτίνης, Καθηγητής, Τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Aθηνών
Δήμητρα Τζέλη, Αναπληρώτρια Καθηγήτρια, Τμήμα Χημείας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Aθηνών
Βασιλική Σαρλή, Αναπληρώτρια Καθηγήτρια, Τμήμα Χημείας, Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης
Οlalla Nieto Faza, Καθηγήτρια, Faculty of Chemistry, University of Vigo, Spain
Γεώργιος. X. Βουγιουκαλάκης, Αναπληρωτής Καθηγητής, Τμήμα Χημείας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Aθηνών
Original Title:
Mechanistic studies of gold-catalyzed reactions between aromatic nitrogen heterocycles and alkynes using Density Functional Theory calculations.
Translated title:
Mechanistic studies of gold-catalyzed reactions between aromatic nitrogen heterocycles and alkynes using Density Functional Theory calculations.
Summary:
In this thesis we studied the mechanism of series of gold catalyzed reactions with the use of DFT (Density Functional Theory) computations.
We studied the gold(I) catalyzed reaction of 1) [4+2] addition reaction of 1,3-diynes with pyrrole and indole rings leading to substituted indoles and carbazoles, respectively 2) [3+2] addition reaction of alkynes onto anthranils that furnishes 7-acylindoles and 3) [3+2] reaction between anthranil, 1,2,4-oxadiazole or 4,5-dihydro-1,2,4-oxadiazole and an ynamide, PhC≡C-N(Ts)Me that produces regioselectively 2-amino-3-phenyl-7-acyl indoles, N-acyl-5-aminoimidazoles or N-alkyl-4-aminoimidazoles, respectively.
For the reaction 1, pathways are found to be significantly more complex than we had anticipated. In the case of carbazoles formation, one competitive route involves the generation of an unexpected spirane intermediate evolving via a 1,2-alkenyl migration. Τhe current study also serves to highlight the importance of fundamental steps that are often disregarded as kinetically irrelevant, such as the protodeauration of reaction intermediates.
For the reactions 2 and 3, the observed regioselectivity seems to be connected to the irreversible formation of a key α-imino gold carbene intermediate, common to all reaction profiles, through the initial regioselective nucleophilic attack of the anthranil N atom onto the alkyne fragment. A subsequent and steep energy drop furnishes the key α-imino gold carbene.
In the case of 1,2,4-oxadiazoles or 4,5-dihydro-1,2,4-oxadiazoles are found, instead of the formation of a five-member ring from the α-imino gold carbene, one competitive route involves the formation of intermediates consisting of a four-member ring condensed with a three-member ring which after a metathesis and ring expansion led to the imidazole ring.
Main subject category:
Science
Number of references:
389
