Olefin, mechanism phase development

Tezacitabine is also an inhibitor of RNDR and it is currently undergoing Phase III development for cancer. Its inhibition mechanism is detailed in Chapter 7. Tezacitabine is synthesized from the cytidine protected at 4 -OH, 5 -OH, and 4-NH2. The Swem oxidation provides a ketone that is converted to a gem-fluoro-sulfonyl olefin with the anion of sulfonylfluorophosphonate. Reduction of the sulfonyl group was realized with Bu3SnH (Figure 8.4). ... 

The accepted mechanism for olefin metathesis proceeds through formation of a metallacyclobutane after olefin coordination to the 14e species. Piers et al. have collected the first evidence for the metallacyclobutane intermediate 19 in the condensed phase [52], The proposed C2V symmetry of this key structure has been predicted by calculations [53] (for related theoretical investigations on olefin metathesis, see [54-57]). Metallacyclobutane formation is likely to determine the regio- and stereochemical outcome of the metathesis reaction, and insight into its geometry is therefore critical in the development of new, selective catalysts. Cycloreversion and olefin dissociation complete the catalytic cycle to re-form the catalytically active species ([Ru] = CH2) which can bind phosphine to re-form the precatalyst or olefin for a subsequent metathesis transformation. 

The olefin metathesis reaction has been proven to be an extremely useful tool for carbon-carbon bond formation in organic synthesis. Owing to the prevalence of this reaction in the synthetic organic literature, it is not surprising that it has been translated to the solid phase. Several metathesis catalysts, for example, A-C, have been developed and employed on the solid support for various applications (Figure 6.1)." Moreover, in several examples, the solid support affords a mechanism for the differentiation of the olefins, allowing the rapid removal of undesirable side products. 

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