Asymmetric Total Synthesis of Tylophorine through a Formal [2+2] Cycloaddition Followed by Migrative Ring Opening of a Cyclobutane

作者：Yamaoka Yousuke^*; Taniguchi Marie; Yamada Ken ichi; Takasu Kiyosei

来源：Synthesis (Germany), 2015, 47(18): 2819-2825.

DOI：10.1055/s-0034-1380430

• heterocycles
• natural products
• cycloaddition
• asymmetric synthesis
• anticancer agents

The asymmetric total synthesis of phenanthroindolizidine alkaloid (-)-tylophorine was achieved by asymmetric transfer hydrogenation of a cyclic imine. The cyclic imine with a pendant phenanthrene core was synthesized by a TfOH-promoted domino ring-contraction/ring-opening sequence of a cyclobutanol bearing an azide group, which was constructed by a formal [2+2] cycloaddition of a 2-vinyl-1,1-biaryl-2-yl ketone enolate. Catalytic asymmetric hydrogenation of the cyclic imine intermediate allowed the late-stage construction of the asymmetric center.

• 出版日期2015-9