Gold catalyzed heterocyclization processes.

The work done in the present doctoral thesis, developed in the GlaxoSmithKline Medicine Research Center Laboratories and in collaboration with the Insubria University of Como, was focused on heterocyclization processes in organic chemistry catalyzed by gold. This metal confirmed its interesting carbophylic properities of activating double and triple carbon-carbon bonds toward various nucleophiles both in inter-and intramolecular way. Three main topics are mainly covered in this work. The first concerns gold catalyzed intramolecular hydroamination of α-aminoallenamides for the preparation of 2-vinylimidazolidinones by means of nucleophilic attack of the amino group on the inside double bond of the diene moiety. This is the first example of gold catalyzed cyclization on allene substrates bearing an amido group which however resulted inactive. The second topic deals with the development of a simple procedure for the intramolecular hydroarylation of N-alkynyl pyrrole-2-carboxamide accomplished by gold(III)-catalysis. The outcome of the reaction led to differently substituted bicyclic pyrrolo-fused products arising either from direct cylization or from a formal rearrangement of the carboxamide group. The substrates containing a propargyl group afforded pyrrolo[2,3-c]pyridine and pyrrolo[3,2-c]pyridine derivatives in a ratio depending on the reaction solvent. When bearing a phenyl group at the C-C triple bond, the pyrrolylamides furnished pyrrolo[2,3-c]azepines and pyrrolo[3,2-c]azepines which ratio depends once again on the used solvent. The last but not the least is aimed on the development of an efficient gold-catalyzed procedure to synthesize 2-alkylidene-3,4-dihydro-2H-1,4-benzoxazines starting from 2-alkynyl-substitued phenols. This is an intramolecular hydroalkoxylation reaction on alkynes tethered to a phenol moiety that represents a valuable alternative to already reported transition-metal-catalyzed procedures.