Carbohydrate carbocyclization by a novel zinc-mediated domino reaction andring-closing olefin metathesis

A general method for carbocyclization of carbohydrates is described using t wo consecutive organometallic transformations: a novel zinc-mediated domino reaction to give functionalized dienes followed by ring-closing olefin met athesis. Ln the first reaction, methyl omega-deoxy-omega-iodo glycosides un dergo reductive elimination with zinc to produce a terminal double bond. Th is also liberates the aldehyde which is immediately alkylated in situ by va rious organozinc reagents. The alkylation occurs under Bart,ief conditions with methylene iodide and several allyl bromides. Zinc plays a dual role by both promoting the reductive elimination and activating: the alkyl halide. Vinylation is carried out by adding divinylzinc. When a new stereogenic ce nter is generated, moderate to excellent stereocontrol is generally observe d. An amino group can be introduced by trapping the intermediate aldehyde a s an inline prior to the alkylation. The reductive elimination-allylation s equence can also be promoted by indium metal. All the alkylations produce a second double bond, and the obtained dienes are subsequently subjected to ring-closing olefin metathesis to produce the corresponding carbocycles. Ne wly developed catalyst 30 with an N-heterocyclic carbene ligand is more rea ctive toward these carbohydrate-derived dienes than commercially available catalyst 18. Acetylation of the free hydroxy groups improves the metathesis reaction significantly. Both five- and six-membered carbocycles are availa ble by this route, including a number of conduritols and quercitols.