Lewis Acid-Mediated Diastereoselective Reduction of N-Protected β-Amino Ketones: Influence of the Nature of the Metal Atom and of the Nitrogen Protecting Group

Lewis acid-mediated chelation and non-chelation control is one of the most fundamental and practical concepts in modern organic chemistry. Extension of these concepts to the reduction of different N-protected α-substituted β-amino ketones indicated that diastereoselectivity in the hydride addition step is strongly dependent on the nature of the metal atom and on the type of protecting group. Strongly chelating TiCl4 and an electron-rich nitrogen protecting group promoted the syn diastereoselectivity in noncoordinating solvents (CH2Cl2) at −78 °C with BH3·py as reducing agent. On the other hand, a Lewis acid as such as CeCl3 and a bulky N-protecting group gave an excess of the anti-diastereomer in coordinating solvents (THF) at the same temperature with lithium borohydride (LiBH4) as reducing agent. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)