Canataxpropellane belongs to the medicinally important taxane diterpene family. The most prominent congener, Taxol, is one of the most commonly used anticancer agent in clinics today. Canataxpropellane exhibits a taxane skeleton with three additional transannular C–C bonds, resulting in a total of six contiguous quaternary carbons, of which four are located on a cyclobutane ring. Unfortunately, isolation of canataxpropellane from natural sources is inefficient. Here, we report a total synthesis of (–)-canataxpropellane in 26 steps and 0.5% overall yield from a known intermediate corresponding to 29 steps from commercial material. The core structure of the (–)-canataxpropellane (2) was assembled in two steps using a Diels–Alder/ortho-alkene-arene photocycloaddition sequence. Enantioselectivity was introduced by designing chiral siloxanes to serve as auxiliaries in the Diels–Alder reaction.
Asymmetric synthesis of a highly functionalized bicyclo[3.2.2]nonene derivative