Total Synthesis of 8,14-Dihydromorphinandienone Alkaloids

A collective synthesis of 8,14-dihydronorsalutaridine, 8,14-dihydrosalutaridine, norisosinomenine, and isosinomenine is reported. The strategy provides direct access to the correct oxidation level of the products. The combination of an organocatalyst guanidine superbase, a tertiary amine base, and a dehydrating agent was necessary for the successful Henry–Michael–dehydration cascade to form the phenanthrene motif. The required selective aliphatic nitro reduction could only be achieved under heterogeneous transfer–hydrogenation conditions.本文报道了8,14-二氢去甲萨鲁他定（8,14-dihydronorsalutaridine）、8,14-二氢萨鲁他定（8,14-dihydrosalutaridine）、去甲异青藤碱（norisosinomenine）与异青藤碱（isosinomenine）的汇聚式合成方法。该策略可直接获得具有正确氧化态的目标产物。为顺利通过亨利-迈克尔-脱水级联反应构建菲骨架，需协同使用胍超强碱有机催化剂、叔胺碱与脱水剂。所需的选择性脂肪族硝基还原反应仅能在非均相转移氢化条件下完成。