Stereoselective synthesis of secondary and tertiary amines through bronsted base assisted mannich, nitro-mannich and a-amination reactions

Résumé

The main objective of this Ph. D. Thesis has been the development of new Brønsted base assisted methodologies for the synthesis of enantiomerically enriched secondary and tertiary amines of synthetic utility and with possible biological activity. First, the enantioselective synthesis of gamma-sulfonyl allyl amines has been developed through a ureidopeptide-based bifunctional Brønsted base catalyzed nitro-Mannich reaction of 2-nitroethyl sulfones with N-Boc imines followed by a nitrous acid elimination. Second, the stereoselective synthesis of pyridine based tertiary and secondary amines has been developed via alpha-amination of 2-cyanoalkyl pyridine N-oxides (JACS 2016, 138, 3282-3285) and Mannich-type reaction of 2-azaaryl acetate N-oxides with N-carbamoyl aldimines (Chem. Eur. J. 2017, 23, 13332-13336), respectively. In both cases, the N-oxide functionality has been employed as a removable activating and stereodirecting group. Finally, during a short stay at Prof. Baran¿s group, a synthetic strategy for the enantio- and diastereoselective modular preparation of trans-disubstituted cyclopropanes has been developed combining cycloaddition and decarboxylative C-C cross-coupling reactions (Nature 2018, 560, 350-354).