Base-Catalyzed Anti-Markovnikov Hydroamination of Vinylarenes – Scope, Limitations and Computational Studies
Horrillo-Martínez, P.; Hultzsch, K. C.*; Gil, A.; Branchadell, V. Eur. J. Org. Chem.; 2007, 3311.
The hydroamination of vinylarenes with primary and secondary amines was studied with catalytic amounts as low as 2 mol-% of LiN(SiMe3)2/TMEDA. Reactions proceeded readily at 120 °C in the absence of solvent to give selective anti-Markovnikov addition. Slow addition was observed at 25 °C with either electron-deficient p-chlorostyrene or secondary cyclic amines such as pyrrolidine, piperidine, or morpholine. Primary amines were prone to a second hydroamination reaction to form tertiary amine byproducts. The selectivity for the mono(hydroamination) products could be improved with a two-fold excess of the amine. KN(SiMe3)2 showed higher catalytic activity but lower selectivity in comparison to that of LiN(SiMe3)2, resulting in undesired C–H-activation byproducts. The mechanism of the lithium-catalyzed hydroamination and the influence of TMEDA was studied with density functional theory.
The hydroamination of vinylarenes with primary and secondary amines was studied with catalytic amounts as low as 2 mol-% of LiN(SiMe3)2/TMEDA. Reactions proceeded readily at 120 °C in the absence of solvent to give selective anti-Markovnikov addition. Slow addition was observed at 25 °C with either electron-deficient p-chlorostyrene or secondary cyclic amines such as pyrrolidine, piperidine, or morpholine. Primary amines were prone to a second hydroamination reaction to form tertiary amine byproducts. The selectivity for the mono(hydroamination) products could be improved with a two-fold excess of the amine. KN(SiMe3)2 showed higher catalytic activity but lower selectivity in comparison to that of LiN(SiMe3)2, resulting in undesired C–H-activation byproducts. The mechanism of the lithium-catalyzed hydroamination and the influence of TMEDA was studied with density functional theory.