A New Copper(I)–Tetrahydrosalen-Catalyzed Asymmetric Henry Reaction and Its Extension to the Synthesis of (S)-Norphenylephrine

✍ Scribed by Yan Xiong; Fei Wang; Xiao Huang; Yuehong Wen; Xiaoming Feng

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 110 KB
• Volume: 13
• Category: Article
• ISSN: 0947-6539
• DOI: 10.1002/chem.200601262

✦ Synopsis

Abstract

A new chiral hydrogenated salen catalyst has been developed for the asymmetric Henry reaction which produces the expected products in moderate to high yields (up to 98 %) with excellent enantioselectivities (up to 96 % ee). A variety of aromatic, heteroaromatic, enal, and aliphatic aldehydes were found to be suitable substrates in the presence of hydrogenated salen 1 f (10 mol %), (CuOTf)~2~**⋅**C~7~H~8~ (5 mol %), and 4 Å molecular sieves. This process is air‐tolerant and easily manipulated with readily available reagents, and has been successfully extended to the synthesis of (S)‐norphenylephrine in 67 % overall yield, starting from commercially available m‐hydroxybenzaldehyde. Based on experimental investigations and MM+ calculations, a possible catalytic cycle including a transition state (8 or A) has been proposed to explain the origin of reactivity and asymmetric inductivity.