Electrophilic and Nucleophilic Activation of Allenamides and Allenoates: Useful Building Blocks in Organic Synthesis

Abstract

The results obtained in the stereoselective manipulation of allene-derivates, particularly allenamides and allenoates were reported in this thesis. The first part is focused on the enantioselective electrophilic activation of allenamides catalysed by BINOL-based Bronsted acids. The catalytic system involved the formation of an α,β-unsatured iminium ion intermediate which then undergoes a nucleophilic attack. Through the use of 2,3-disubstituted indoles as nucleophiles, a highly enantioselective synthesis of indolenine and indoline compounds was developed. An enantioselective intramolecular Friedel-Craft cyclization of allenamides, bearing electron-rich aromatic rings in order to obtain enantioenriched tetrahydroisoquinoline compounds, was further illustrated. The second part is centered on the manipulation of allenoates. In particular, through gold–catalysed [3,3]-sigmatropic rearrangements of propargylic carboxylates, the corresponding allenoate can be formed in situ. The intrinsic nucleophilicity of the latter was used to develop an efficient direct gold-catalysed α-allylation of enones, using alcohols as alkylation agents. Finally, a chapter regarding the manganese-catalysed C‒H-alkynylation of indoles was reported using readily available 1-bromo-alkynes. The methodology proved to be tolerant in the presence of challenging aryl- and alkyl-bromo-alkynes. An efficient method for the synthesis and the modification of peptides was indeed reported.