Enantiospecific Total Synthesis of Natural (+)-Taxusin. 2. Functionalization of the A-Ring and Arrival at the Target

A total synthesis of (+)-taxusin (1) has been realized by virtue of the development of a practical route for complete functionalization of the A ring. To achieve this goal, it proved necessary to devise a strategy that would enable chemical transformations to proceed in a very congested environment. The successful pathway from 2 required 19 steps consisting principally of chemoselective oxidation and reduction maneuvers of various types. The requisite methyl substituent was introduced by 1,2-addition of the methylcerate reagent to a C(12) ketone intermediate. Several tactics that ultimately proved unsatisfactory are also discussed in an effort to set important boundary limits on chemical reactivity. The pivotal roles played by samarium diiodide and tetrapropylammonium perruthenate in permitting the deployment of appropriate chemical changes are noteworthy.