Reductive dealkoxyhalogenation

A useful and simple method for the one-pot preparation of highly functionalized, enantiomerically pure cyclopentanes from readily accessible carbohydrate precursors has been designed by Chiara and coworkers [73]. The procedure depends on a samarium(II) iodide-promoted reductive dealkoxyhalogenation of 6-desoxy-6-iodo-hexopyranosides such as 7-160 to produce a 6,e-unsaturated aldehyde which, after reductive cyclization, is trapped by an added electrophile to furnish the final product. In the presence of acetic anhydride, the four products 7-161 to 7-164 were obtained from 7-160. 

The reductive dealkoxyhalogenation of some 6-iodopyranoses and 5-iodofuranoses using zinc-silver/graphite complex has been described (Scheme 19). In the latter series some alternative reactions are observed (see also Vol. 24, p.l60). 

In order to effect the overall ring contraction, two complete reaction sequences are necessary. These include a reductive dealkoxyhalogenation to give the ring-opened hex-5-enal followed by an intramolecular ketyl-olefin reductive coupling, to afford the ring contracted organosamarium intermediate. A complete mechanism for the two individual subsequent steps is depicted in Scheme 3.30. 

After the dealkoxyhalogenation, the mechanism of the Sml2-mediated cyclization of the intermediate aldehyde is shown in Scheme 3.32. The process is probably initiated by a single electron reduction of the aldehyde to form a ketyl radical, followed by an exo-cyclization onto the double bond. The resulting primary radical undergoes cyclization onto the tethered alkyne and the highly reactive vinyl radical that results is quenched by abstraction of a hydrogen atom from the solvent [68]. 

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