Enantioselective formal synthesis, 4-demethoxydaunomycin

Sekine, A. Ohshima, T. Shibasaki, M. (2002) An enantioselective formal synthesis of 4-demethoxydaunomycin using the catalytic asymmetric ring opening reaction of meso-epoxide with p-anisidine.. Tetrahedron, 58 75-82. 

During the enantioselective formal synthesis of 4-demethoxydaunomycin, BuLi proves to be the base of choice for a Hofmann elimination process of the quaternary ammonium salt of a trans-p-aimno alcohol to obtain the corresponding allyhc alcohol with a slight erosion of ee (eq 61). Other bases such as KHMDS and KOtBu afford 1,4-dimethoxy-naphthalene as a result of an undesired consequent dehydration. 

The enantioselective formal total synthesis of 4-demethoxydaunomycin was accomplished in the laboratory of M. Shibasaki. The key intermediate was prepared from an enantiomerically enriched frans- 3-amino alcohol, which was first exhaustively methylated to the corresponding quaternary ammonium salt. This salt was then treated with excess n-BuLi to afford the desired allylic alcohol in moderate yield. 

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