H-bonding vs Protonation of Alkynes in Regioselective Hydroamination Reactions: A Glimpse into the Reactivity of Arylogous Ynolethers and Ynamines
Résumé
In this paper is described the competition and transition between hydrogen bonding and protonation of alkynes connected, on one side, to various aromatic rings and to chiral amino ester appendages on the other side. While the first mode of activation induced the cyclization into pyrrolidines, the protonation of the alkyne led preferentially to tetrahydropyridines due to the higher level of the highest occupied molecular orbital (HOMO) of the considered arylogous ynolethers and ynamines. The transition between H-bonding and protonation was observed with the alkyne substituted with 2-methoxyphenyl, for which the cyclization delivered either five- or six-membered rings depending on the temperature of the experiment. From there, the cyclization of dialkoxy- and trialkoxyphenyl-substituted alkynes into six-membered rings, i.e., tetrahydropyridines, was developed. When next applied to alkynylindoles, the same pattern of cyclization provided six-membered rings as an illustration of the reactivity of arylogous ynamines. Thanks to the high reactivity of the intermediate cationic species, weak nucleophiles such as NH-oxazolidinone participated efficiently in the hydroamination reaction of alkynylindoles. Pyrrolidines, tetrahydropyridines, and piperidines decorated with various aromatics and substituents were thus prepared in enantio- and stereoselective manner. Capitalizing on the enamine moiety of the azaheterocycles, the molecular diversity was extended through stereoselective oxidation and ring contraction processes.