If the ability of the pharmaceutical industry to produce a given agent at acceptable cost is to keep pace with the current exciting growth in understanding of fundamental biological processes, an ongoing fruitful interaction between natural product synthesis and other exploratory efforts across the broad range of chemistry and biochemistry must be maintained. An obvious deficit in current natural product synthesis is the small number of generally useful methods for the construction of cyclic systems with control of absolute configuration. Intramolecular insertion of an alkylidene carbene into the C-H bond of a configurationally defined ternary center should be a general strategy for the construction of enantiomerically-pure natural products having cyclic quaternary centers. An exploration of this strategy is proposed, with a particular focus on the development of an efficient process for the enantioselective preparation of the highly functionalized 6-8-6 ring system of the clinically-promising antineoplastic diterpene taxol.
