Calculations on the Ruthenium-Catalyzed Diene and Dienyne Ring-Closing Metathesis Reactions in the Synthesis of Taxol Derivatives.

Density-functional and semiempirical calculations (M06, M06L, and PM6) on intermediates in the ring-closing metathesis (RCM) reactions in the synthesis of Taxol derivatives give results in excellent agreement with the results of previous experimental work. The results suggest that the degree of steric overloading plays a decisive role in determining the outcome (ene-ene or ene-yne-ene metathesis). Due to the rigidity of the Taxol skeleton being formed in the ene-yne-ene cascade reaction, the transition states in its final ene-ene metathesis reaction stage are particularly sensitive to steric effects.

Chagosensine: A Riddle Wrapped in a Mystery Inside an Enigma.

The marine macrolide chagosensine is supposedly distinguished by a ()-configured 1,3-chlorodiene contained within a highly strained 16-membered lactone ring, which also incorporates two -2,5-disubstituted tetrahydrofuran (THF) rings; this array is unique. After our initial synthesis campaign had shown that the originally proposed structure is incorrect, the published data set was critically revisited to identify potential mis-assignments. The "northern" THF ring and the -configured diol in the "southern" sector both seemed to be sites of concern, thus making it plausible that a panel of eight diastereomeric chagosensine-like compounds would allow the puzzle to be solved.

Total Synthesis of Putative Chagosensine.

The marine macrolide chagosensine is the only natural product known to date that embodies a Z,Z-configured chloro-1,3-diene unit. This distinguishing substructure was prepared by a sequence of palladium-catalyzed 1,2-distannation of an alkyne precursor, regioselective Stille cross-coupling at the terminus of the resulting bisstannyl alkene with an elaborated alkenyl iodide, followed by chloro-destannation of the remaining internal site. The preparation of the required substrates centered on cobalt-catalyzed oxidative cyclization reactions of hydroxylated olefin precursors, which allowed the 2,5-trans-disubstituted tetrahydrofuran rings, embedded into each building block, to be formed with excellent selectivity.

Site-Selective trans-Hydrostannation of 1,3- and 1,n-Diynes: Application to the Total Synthesis of Typhonosides E and F, and a Fluorinated Cerebroside Analogue.

Propargyl alcohols are privileged substrates for stereochemically unorthodox trans-hydrostannation reactions catalyzed by [Cp*RuCl] (Cp*=pentamethylcyclopentadienyl), because an incipient hydrogen bond between the -OH group and the polarized [Ru-Cl] unit assists substrate binding. For this very reason, it is also possible to subject diyne derivatives carrying one -OH group to site-selective stannylation, even if the acetylene units are conjugated and hence, electronically coupled. An unusual temperature dependence was observed in that heating tends to improve site-selectivity, whereas per-stannylation is favored when the reaction is carried out in the cold.

Study of Cascade Ring-Closing Metathesis Reactions en Route to an Advanced Intermediate of Taxol.

A highly functionalized intermediate in the synthesis of Taxol has been synthesized, which features the tricyclic core and the required oxygen substituents at C1, C2, C7, C10, and C13. The key step, a ring-closing dienyne metathesis (RCDEYM) reaction, has been thoroughly optimized to favor the tricyclic product over the undesired bicyclic product resulting from diene metathesis.

Cascade Metathesis Reactions for the Synthesis of Taxane and Isotaxane Derivatives.

Tricyclic isotaxane and taxane derivatives have been synthesized by a very efficient cascade ring-closing dienyne metathesis (RCDEYM) reaction, which formed the A and B rings in one operation. When the alkyne is present at C13 (with no neighboring gem-dimethyl group), the RCEDYM reaction leads to 14,15-isotaxanes 16 a,b and 18 b with the gem-dimethyl group on the A ring. If the alkyne is at the C11 position (and thus flanked by a gem-dimethyl group), RCEDYM reaction only proceeds in the presence of a trisubstituted olefin at C13, which disfavors the competing diene ring-closing metathesis reaction, to give the tricyclic core of Taxol 44.

Highly efficient synthesis of the tricyclic core of Taxol by cascade metathesis.

An efficient enantioselective synthesis of the ABC tricyclic core of the anticancer drug Taxol is reported. The key step of this synthesis is a cascade metathesis reaction, which leads in one operation to the required tricycle if appropriate fine-tuning of the dienyne precursor is performed.