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

A general method for carbocyclization of carbohydrates is described using two consecutive organometallic transformations: a novel zinc-mediated domino reaction to give functionalized dienes followed by ring-closing olefin metathesis. Ln the first reaction, methyl omega-deoxy-omega-iodo glycosides undergo reductive elimination with zinc to produce a terminal double bond. This also liberates the aldehyde which is immediately alkylated in situ by various 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 center is generated, moderate to excellent stereocontrol is generally observed. An amino group can be introduced by trapping the intermediate aldehyde as an inline prior to the alkylation. The reductive elimination-allylation sequence 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. Newly developed catalyst 30 with an N-heterocyclic carbene ligand is more reactive 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 available by this route, including a number of conduritols and quercitols.