2-(Aminomethyl)-oxazolines:  Highly Modular Scaffolds for the Preparation of Novel Asymmetric Ligands

Abstract

Highly modular chiral 2-(aminoalkyl)oxazolines have been prepared from alpha-amino acids and 1,2-amino alcohols. The amine-functionalized oxazolines were employed as scaffolds in the preparation of a number of different ligands with potential denticities varying from 2 to 5. The obtained ligands were employed and evaluated in the ruthenium-catalyzed asymmetric transfer-hydrogenation of acetophenone and in the titanium-catalyzed addition of diethylzinc to aldehydes. In the latter process, enantioselectivity up to 97% was obtained.

Oxazoline‐Based Organocatalyst for Enantioselective Strecker Reactions: A Protocol for the Synthesis of Levamisole

“…Finally, oxazoline catalysts 1 a-j were prepared by cyclization of the corresponding amides III in the presence of a catalytic amount of 4-dimethylaminopyridine (DMAP). [22] A single crystal of organocatalyst (S,S)-1 j obtained from dichloromethane/hexanes (1:2) was subjected to X-ray structure analysis [23] (Scheme 1). Characterization data are given in the Supporting Information, which proved useful for understanding the structures of intermediates involved in the Strecker reaction.…”

Stereochemical Consequences of Threefold Symmetry in Asymmetric Catalysis: Distorting C3 Chiral 1,1,1‐Tris(oxazolinyl)ethanes (“Trisox”) in CuII Lewis Acid Catalysts

“…1 H NMR (CDCl 3 , 400 MHz): d = 1.26 (m,9 H;CH 3(ethyl) , CH 3(future oxa) ), 1.41 (s,6 H;CH 3(bridge) 5 H;CH (arom) ); 13 C { 1 H} NMR (CDCl 3 , 100 MHz): d = 23.7,23.8 (CH 3(bridge) ) 24.0, 24.5 (CH 3 ), 50.0 (C quat(bridge) ), 55.7 (C quat(methyl side) ), 55.9 (CH), 66.2 (CH 2(phenyl side) ), 69.6 (CH 2(methyl side) ), 126. 4,128.0,128.9 (CH (arom) 1-{(4 R)-4-Phenyloxazolin-2-yl}-1-(4,4-dimethyloxazolin-2-yl)-1-methylethane [22] (Ph-dm-BOX): SOCl 2 (0.80 mL, 10.9 mmol) was added dropwise to a cooled solution (0 8C) of N-{(R)-2-hydroxy-1-phenylethyl}-N'-(2-hydroxy-1,1-dimethylethyl)-dimethylmalonamide (737 mg, 2.29 mmol) in CH 2 Cl 2 (150 mL). The reaction mixture was stirred overnight at ambient temperature, cooled to 0 8C and quenched by addition of aqueous NaHCO 3 (65 mL).…”

Ruthenium‐Catalyzed Enantioselective Reduction of Electron‐Rich Aryl Alkyl Ketones

“…[8] Inspired by the results obtained by Zhang, we investigated the catalytic ability of a number of ruthenium complexes based on N-functionalized 2-aminomethyloxazoline derivatives. [9] The results were rather poor, but interestingly we found that a Boc-protected amino acid hydroxy-amide, a precursor to the 2-aminomethyloxazolines, acted as an efficient ligand in the transfer hydrogenation. The combination of [RuCl 2 A C H T U N G T R E N N U N G (p-cymene)] 2 and ligands 1 or 2 generated ruthenium complexes which catalyzed the reduction of aryl alkyl ketones in good yield and in excellent enantioselectivity.…”