Synthesis of Chiral Nonracemic 1-(2-Pyridinyl)ethylamines:  Stereospecific Introduction of Amino Function onto the 2-Pyridinylmethyl Carbon Center

Abstract

Stereospecific substitutions of optically pure 1-(pyridinyl)ethyl methanesulfonates with various amines are described. The reaction of (R)- or (S)-1-(2-pyridinyl)ethyl methanesulfonate with primary amines, including amino acid esters, gives N-substituted (S)- or (R)-1-(2-pyridinyl)ethylamines (4) with inversion of the configuration. Secondary cyclic amines are also reacted with (R)-2 to give the corresponding substituted amines (5) in excellent yields. Optically pure and meso triamine ligands having two pyridine rings, (S,S)-4f and meso-4f, (S,S)-9e, (S,R)-9e, and (S,S)-9f, have been prepared in stereochemically pure form by this method. Not only the substitution reaction of optically active 2 but also that of 1-(4-pyridinyl)ethyl and 1-(3-pyridinyl)ethyl methanesulfonates 11 and 14 take place stereospecifcally with inversion of the chiral center.

B(C6F5)3-Catalyzed Asymmetric Reductive Amination of Ketones with Ammonia Borane

“…GC (for program, see Experimental Section (general method)): retention time [min]: major ( S,S )- 3ta isomer, 8.6; minor ( R,S )- 3ta isomer, 8.9. The NMR data of ( S,S )- 3ta match those reported in the literature …”

“…The NMR data of (S,S)-3ta match those reported in the literature. 22 1 H NMR (600 MHz, CDCl 3 ) δ 8.52−8.51 (m, 1H), 7.52−7.50 (m, 1H), 7.23 (t, J = 7.8 Hz, 2H), 7.20−7.13 (m, 3H), 7.07−7.06 (m, 1H), 6.98 (d, J = 7.8 Hz, 1H), 3.52 (q, J = 6.6 Hz, 1H), 3.37 (q, J = 6.6 Hz, 1H), 1.22 (d, J = 6.6 Hz, 3H), 1.20 (d, J = 6.6 Hz, 3H); 13 (S)-4-Phenyl-N-((S)-1-phenylethyl)butan-2-amine (3ua). Colorless viscous liquid, 82% yield, 104.1 mg; 86% de.…”

Increased Enantioselectivity and Remarkable Acceleration of Lipase‐Catalyzed Transesterification by Using an Imidazolium PEG–Alkyl Sulfate Ionic Liquid

“…We further discovered a very interesting activation property of IL 1-PS: the acceleration of the rate was significantly dependent on the substrates (Table 4). A truly remarkable acceleration was accomplished for 1 a, 1 b, 1 d, [29] 1 e, [30] 1 h, [33] 1 k, [36] and 1 i; [35] 1100-fold acceleration was obtained for alcohol, (AE ) 32] and 1 j, [35] and none was observed for 1 c [28] or 1 f. [31] The effect of IL 1 on the enantioselectivity was also dependent on the substrate: a remarkably increased enantioselectivity was obtained for 1 a, 1 j, and 1 l, while only a small modification occurred for 1 b.…”

Transaminases and their Applications

“…Their use as building blocks in pharmaceuticals, like in antiarrhythmic, cancer-or diabetes-treating drugs, and agrochemicals, makes it particularly important to find enzymatic approaches for their production and to overcome the chemical synthesis of chiral amines, which requires protective groups, toxic transition metal catalysts, harsh reaction conditions, and multireactions [29][30][31][32]. Reactions catalyzed by transaminases offer advantages like a promiscuous substrate spectrum, no need for external cofactors, high enantio-and stereoselectivity, mild reactions conditions, and good reaction yields.…”