Enantioselective Formation of tert-Alkylamines by Desymmetrization of 2-Substituted Serinols

• Published in: Chemistry : a European journal 2008-04, Vol.14 (11), p.3290-3296
• Main Authors: Hong, Mi Sook, Kim, Tae Woo, Jung, Byunghyuck, Kang, Sung Ho
• Format: Article
• Language: English
• Subjects: alkylamines; Amines - chemical synthesis; desymmetrization; Lewis acids; Magnetic Resonance Spectroscopy; organic chemistry; Propanolamines; Propylene Glycols - chemistry; Spectrometry, Mass, Electrospray Ionization; Stereoisomerism; stereoselectivity
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200701875

Novel enantioselective desymmetrization of 2‐substituted 2‐amino‐1,3‐propanediols has been established to generate asymmetric quaternary carbon centers comprising an amino group. Enantioselective as well as chemical conversion proved to be greatly dependent on the protecting group of the amino group in the substrate, desymmetrizing reagent, base, solvent, and naturally, catalyst. The highly effective desymmetrization has been implemented by using N‐benzoylated substrates with benzoyl chloride and triethylamine in the presence of tetraphenylbisoxazoline (24)–CuCl2 complex in THF at ambient temperature. An extensive survey of catalysts revealed that dimethylmalonate‐bridged bisoxazoline–CuCl2 complexes were superior. Among them, the tetraphenylbisoxazoline (24)–CuCl2 complex turned out to work most efficiently with a wide array of the substrates. All the examined substrates, with the exception of 2‐phenylserinol 36, were desymmetrized in the presence of 24–CuCl2 complex to give high enantioselectivities ranging from 85 to 95 % ee. Complementary use of the diisopropylbisoxazoline (22)–CuCl2 complex has remedied the mediocre desymmetrization of 36 to give a significantly improved enantioselectivity from 63 to 83 % ee. Enantioselective desymmetrization: Novel enantioselective desymmetrization of 2‐substituted serinols has been established to generate asymmetric quaternary carbon centers comprising an amino group. All the examined substrates, with the exception of 2‐phenylserinol, were desymmetrized with 85 to 95 % ee when using tetraphenylbisoxazoline–CuCl2 complex (see scheme; ee=enantiomeric excess).