The Synthesis of (±)‐11‐Deoxydaunomycinone via Regioselective Tandem Diels ‐ Alder Reactions

The 2,5‐dimethylidene‐3,6‐bis[( Z )‐(2‐nitrophenyl)sulfenylmethylidene]‐7‐oxabicyclo[2.2.1]heptane ( 13 ) can be used to generate polyfunctional and multicyclic molecules with high regio‐ and stereoselectivity via two successive Diels ‐ Alder additions using two different dienophiles. This principle has been applied to the synthesis of (±)‐11‐deoxydaunomycinone ( 7 ), the aglycone of an important antitumor drug. The 2,3‐didehydroanisole adds to 13 and gives the monoadduct 14 with high regioselectivity. No trace of bis‐adduct is observed. The 1,4‐epoxy‐1,2,3,4‐tetrahydro‐5‐methoxy‐3‐methylidene‐2‐[( Z )‐(2‐nitrophenyl)sulfenylmethylidene]anthracene ( 15 ) obtained on treating 14 with K 2 CO 3 adds to methyl vinyl ketone to give [(1 RS , 2 SR , 5 RS ,12 RS )‐5,12‐epoxy‐1,2,3,4,5,12‐hexahydro‐7‐methoxy‐1‐(2‐nitrophenyl)sulfenyl‐2‐naphthacenyl]methyl ketone ( 16 ) with high regio‐ and stereoselectivity. The acid‐catalyzed 7‐oxanorbornadiene→phenol rearrangement of 16 is regioselective and gives (5‐acetoxy‐3,4‐dihydro‐7‐methoxy‐2‐naphthacenyl) methyl ketone ( 20 ) which was transformed into (±)‐7,11‐dideoxydaunomycinone ((±)‐ 24 ), a known precursor of 7 .