Total synthesis of (-)-lentiginosine (1) was achieved in nine steps from (3R, 4R)-3,4-dihydroxy-1,5-hexadiene (2). Cross metathesis, vinyl addition and DDQ oxidation were applied to generate the key 3-oxonona-1,4,8-triene 6, which was cyclised to 4-oxopiperidine 7 by diastereoselective double aza-Michael reaction. Both theoretical and empirical studies support that the stereochemical assignment of the major Michael adduct is the desired (2R)-4-oxopiperidine 7.
