Effect of Additives in the Hydroamination/Cyclization of Aminoalkenes Catalyzed by a Binaphtholate Yttrium Catalyst

Abstract

A series of various solvents and additives were tested in enantioselective hydroamination/cyclization reactions of aminoalkenes catalyzed by a binaphtholate yttrium catalyst. The functional group tolerance of the catalyst and the influence on the reaction rate and enantioselectivity was studied. Some weakly coordinating polar solvents, such as Et2O, MTBE, and chlorobenzene led to slightly increased reaction rates compared to the less polar solvent benzene, presumably due to a better stabilization of the polar transition state. Stronger binding solvents and additives, such as THF, DMAP, pyrrolidine, n‐propylamine, and 1‐phenylethylamine, decrease the reaction rate and diminish the enantioselectivity of the hydroamination product. Some additives, such as THF, Et2O, MTBE, chloro‐ and bromobenzene, as well as (+)‐sparteine resulted in slightly higher enantioselectivities in the cyclization of the model substrate C‐(1‐allylcyclohexyl)methylamine, although this observation was not generally true for other aminoalkene substrates. The reaction rates and enantioselectivities were depressed in the presence of (−)‐sparteine using the (R)‐binaphtholate‐ligated catalyst. In case of C‐(1‐allylcyclohexyl)methylamine, the enantioselectivity was switched from 76% ee favoring the (S)‐enantiomer of the hydroamination product when using (+)‐sparteine to 22% ee in favor of the (R)‐enantiomer when (−)‐sparteine was used. The rates of cyclization of aminoalkenes and the resulting enantioselectivities significantly depend on substrate concentration with the highest rate (13.6 h−1) and enantioselectivity (68% ee) observed in dilute conditions (0.05 M) compared to a concentrated solution (0.5 M, 5.0 h−1, 35% ee) for 2,2‐dimethylpent‐4‐enylamine. These observations indicate that the reaction mechanism is shifted in favor of a slower, less enantioselective catalytic cycle involving a higher coordinate species when higher substrate concentrations or stronger binding additives are present.

Silyl‐Substituted ortho‐Terphenoxide Group 3–5 Complexes: Synthesis, Structure and Applications in Catalysis

“…Thereafter, catalyst stock solution (20 μL–50 μL for 2 or 5 mol% respectively) was added and the conversion was monitored via 1 H‐NMR spectroscopy by following the disappearance of the olefinic signals of the substrate and the appearance of the signals of the product. 1 H and 13 C NMR spectra of the products are in agreement with the literature [8d] …”

Yttrium‐Catalyzed Intermolecular Anti‐Markovnikov Hydroamination and Sequential Intermolecular Hydroamination/Endocyclization of Vinylsilanes

“…Moreover, in a 1:1 mixture of sterically hindered (unreactive) tert‐ butylamine and n ‐octylamine (Figure S5), full conversion of n ‐octylamine to the hydroamination product was obtained within 1.5 h compared to 5 h when using pure n ‐octylamine. Recently, we have reported the effect of additives on the rate and enantioselectivity on the hydroamination/cyclization of aminoalkenes, [37] indicating that polar additives can stabilize the polar cyclization transition state and increase the reaction rate. However, contrary to our current findings, addition of stronger binding additives, such as pyrrolidine and n ‐propylamine actually resulted in a decrease in reaction rate of the intramolecular process.…”

Iridium(III)‐Catalyzed Intermolecular C(sp3)‐H Amidation for the Synthesis of Chiral 1,2‐Diamines

“…In particular, cationic Ti IV ‐ or Zr IV ‐based catalysts are very appealing, due to the abundant nature of these metals and their excellent Markovnikov selectivity in the considered transformation (Table 1, entries 2–3). Indeed, group‐IV metals have been known to promote or catalyze intramolecular hydroaminations of aminoalkenes since the 2000’s [21] . Moreover, Ti‐catalyzed intermolecular hydroamination of styrenes with electron‐deficient anilines was reported by Ackermann and co‐workers in 2005 [22] .…”