Sulfide contraction reaction

The synthesis of thiiranes with subsequent elimination of sulfur is an important procedure for the creation of C=C bonds, especially for sterically crowded systems (47,48), in analogy to the Eschenmoser-sulfide-contraction reaction (116). The spontaneous elimination of sulfur was observed in the rhodium-catalyzed reaction of diazo compound 62, which gave rise to the formation of cyclopentenone derivative 63 (117) (Scheme 5.24). A synthesis of indolizomycin was published by Danishefsky and co-workers (118) and involved a similar annulation step. In this case, however, the desulfurization reaction was achieved by treatment with Raney Ni. 

A third application of the Eschenmoser reaction in the synthesis of racemic perhydrogephyrotoxin (76) is based on an extension of the chemistry developed during the pumiliotoxin C synthesis. - Beginning with the bicyclic thiolactam (73), the sulfide-contraction reaction was used to append to the decahydro-isoquinoline a functionalized five-carbon side chain that would later be cyclized and become the a-hy-droxyethylpyrrolidine portion of the molecule. Alkylation of the thiolactam (73) with methyl 5-bromolevulinate followed by treatment with the Eschenmoser dual base-thiophile reagent (28) produced the vinylogous carbamate (74) in 81% yield from the starting thiolactam (73 Scheme 17). Reduction of the vinylogous amide (74), followed by equilibration of the amino ketones in the presence of... 

A series of carbapenams have been generated using the sulfide-contraction reaction to construct the constituent -amino acid segment. The thiopyroglutamate derivative (143) was condensed with ethyl 2-bromoacetoacetate in the presence of sodium bicarbonate to afford the a-acyl vinylogous carbamate (144 Scheme 31). The use of sodium bicarbonate in the sulfide contraction was critical in this particular... 

The foregoing conditions were applied successfully in the synthesis of diplodialide A (175 Scheme 37). Since earlier studies had demonstrated that the sulfide-contraction conditions were not compatible with a,3-unsaturated thioamides, the 3-acetoxy precursor (173) was used instead. The intramolecular sulfide-contraction reaction successfully accomplished the cyclization to generate the P-keto lactone (174) in modest yields. Elimination of the acetoxy group yielded diplodialide A (175). 

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