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.

The 5‐endo‐tet cyclization/ring opening of aziridine (I) proceeds smoothly in the presence of HF/MeCN to afford tetrahydrofuran (II), which in turn is further elaborated to ent‐(‐)‐pachastrissamine (IV).