The convenient enantioselective synthesis of nebivolol (1) was described. The key steps of this total synthesis were based on a Sharpless asymmetric epoxidation methodology employing 4-fluoro-2-(5- hydroxypent-3-enyl)phenol (2) as a substrate and the efficient formation of (2S,1R)-2-(2-amino-1-hydroxy ethyl)-6-fluorochroman (6) and (R,R)-6-fluoro-2-oxiranyl-chroman (10). Simultaneously, the approach was inves-tigated for the nucleophilic ring opening of epoxide 10. Finally, 10 was afforded in an ex-cellent yield and the ring cleavage of 10 led to the formation of 1 in a 14.1% overall yield over steps after optimization of the steps which accompanied a 2.1% overall yield in literature.

Key words: Sharpless asymmetric epoxidation, nebivolol, hypertensive agent