Asymmetric Syntheses of 2-(1-Aminoethyl)phenols

✍ Scribed by E. Peter Kündig; Candice Botuha; Gilles Lemercier; Patrick Romanens; Lionel Saudan; Sylvie Thibault

• Book ID: 102257226
• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: German
• Weight: 278 KB
• Volume: 87
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200490054

✦ Synopsis

Abstract

Three different routes were probed for the synthesis of enantiomerically enriched 2‐(1‐aminoethyl)phenols and their methyl ethers. The first route centers on diastereoselective nucleophile addition to chiral imines. The second route has as key steps the enantioselective reduction of a ketone followed by nucleophilic substitution, and the third route involves a diastereoselective imine reduction. The efficiency of the approach depends on the substrate substitution pattern. All three methods work well for the parent compound 2‐(1‐aminoethyl)phenol (1) but the third route is the most efficient, providing the compound with >96% enantiomer excess in three steps with an overall yield of 71%. Conversely, for the ortho‐methyl analogue 2, the first method is best. For the t‐Bu‐substituted analogue 3, only moderate enantiomeric enrichment was achieved.