Construction of Quaternary Carbon Stereocenter of α‑Tertiary Amine through Remote C–H Functionalization of Tris Derivatives: Enantioselective Total Synthesis of Myriocin

We describe the development of a strategy for the construction of the quaternary carbon stereocenter of α-tertiary amines. This strategy highlights a site-selective C–H functionalization involving an alkoxy-radical-triggered 1,5-hydrogen transfer (1,5-HAT) reaction of a conformationally fixed spiro-compound derived from trishydroxymethylaminomethane (Tris). The utilization of this strategy enabled an enantioselective total synthesis of myriocin, a naturally occurring sphingosine analog that displays potent immunosuppressive activity.