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

Abstract

AbstractThe 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 K2CO3 adds to methyl vinyl ketone to give [(1RS, 2SR, 5RS,12RS)‐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.