RDG-Controlled Organic Synthesis

    A long term goal is the combination of reactions controlled by reagent-directing groups (RDG) in a synthetic sequence.[47] In an ideal scenario such a RDG would not only control selectivity of a single transformation but also for a sequence of reactions introducing structural elaborations A-B-C until it is finally removed from the product. This removal step (reagent d) would be most ideal if it could be incorporated in the course of a further skeleton expanding operation, which at best would be a fragment coupling step at a late stage of a synthesis.

Scheme 3: Concept of RDG-controlled Organic Synthesis.

    The first realization of this concept has been achieved within the context of an enantioselective total synthesis of (R,R,R)-α-Tocopherol. The synthesis plan is outlined in Scheme 4.[90]

Scheme 4: RDG-controlled enantioselective total synthesis of (R,R,R)-α-Tocopherol.

    More recently, we demonstrated the efficiency of the RDG-controlled synthesis by realizing a general synthetic strategy for the enantioselective construction of lycopodium alkaloids, which are important components in traditional chinese medicine.[124] Thus, core of the synthesis is a reaction sequence consisting of directed hydroformylation/intramolecular carbonyl ene reaction and a second directed hydroformylation (see Scheme 5) demonstrating the power of stereoselective catalytic carbon-carbon bond formation for total synthesis.

Scheme 5: RDG-controlled enantioselective total synthesis of lycopodium alkaloids.