The development of new ruthenium-catalyzed reactions and a new strategy for cyclopentenone synthesis.

다국어 초록 (Multilingual Abstract)

A number of new ruthenium catalyzed carbon-carbon bond forming reactions have been developed. Cyclopentadienyl ruthenium (II) complexes catalyze the addition of a halide, an alkyne and an enone to form vinyl halides in a three component coupling process. Depending on the conditions utilized, either the <italic> Z</italic> or <italic>E</italic> isomer can be formed selectively. If sterically bulky alkynes are used, completely selective formation of the <italic>Z</italic> isomer of the vinyl halide is seen. When an aldehyde is added to the reaction mixture, a four component coupling is achieved, wherein a highly functionalized aldol adduct is obtained with control of both olefin selectivity and diastereoselectivity in the aldol reaction.
The synthetic utility of the vinyl halides is demonstrated by their use as cross coupling partners in Suzuki-type reactions, as synthons for α-hydroxy ketones <italic>via</italic> epoxidation or dihydroxylation, or as precursors to 2,3-disubstituted cyclopentenones <italic>via</italic> a Nozaki-Kishi reaction followed by an oxidative rearrangement. The efficiency of this strategy for cyclopentenone synthesis is demonstrated by the total syntheses of tetrahydrodicranenone B, an antimicrobial fatty acid (in 7 linear steps and 14% overall yield), rosaprostol, an antiulcer drug (in 7 linear steps and 31% overall yield) and a potent COX-2 inhibitor (in 5 linear steps and 30% overall yield).
Cyclopentadienyl ruthenium (II) complexes also catalyze the addition of an allene and an enone to form 1,3-dimes in a two component coupling. When allenes bearing a hydroxyl group juxtaposed 4 or 5 carbons from the internal terminus of the allene are used, cyclic ethers are obtained. A wide variety of bicyclic ethers can also be formed from this reaction. When strong Lewis acid cocatalysts are added, secondary amines can function as nucleophiles, giving. both pyrrolidine and piperidine products.