Samarium-mediated fragmentation

Before giving up oti the samarium-mediated fragmentation approach, we decided to investigate one additional substrate that would not be able to form a cyclobutane because one of the 1,4-dicarbonyl partners was an ester (186, Scheme 35). The requisite substrate was readily accessed by converting aldehyde 186 to carboxylate 187 using a Pinnick oxidation followed by treatment with TMS diazomethane. Ketone 186 reacted with samarium diiodide but no fragmentation took place, only reduction of the ketone to a mixture of secondary alcohol products, one of which further reacted to form lactone 189. 

It is well known that transition metal-catalyzed carbon-carbon bond formations are extraordinarily difficult with sterically hindered, electron-rich aryl triflates.However, just such a transformation was required to install the Z-propenyl fragment necessary for the samarium-mediated cyclization. Lauren s initial attempts to achieve this goal afforded predominantly detriflated material and capricious reactions leading to loss of biaryl enantiopurity. 

This radical cyclization strategy was utilized for the synthesis of the smaller fragment silyl ether 54 as well (Scheme 8). Evans aldol reaction of the boron eno-late derived from ent-32 with aldehyde 33, samarium(III)-mediated imide methyl ester conversion, and protecting group exchange led to tosylate 51. Elaboration of 51 to ketone 53 was achieved under the conditions used for construction of the second tetrahydrofuran moiety of 49 from 46. A highly diastereoselective reduc-... 

The retrosynthetic approach to welwitindolinone A isonitrile (6) used by the Wood group is shown in Scheme 33. After recognition of the possibility of deriving the vinyl isonitrile fragment from a ketone, the disconnection of 6 to 140 was proposed. A literature report of a samarium (II) iodide-mediated reductive coupling of acrylates with isocyanates to give amides, which could be expected to lead to a new spirooxindole synthesis, prompted the disconnection of 140 to 141. This compound was to be obtained from the readily available cyclohexadiene derivative 143, by way of bicyclic ketone 142. 

Samarium Diiodide-Mediated Carbanion Fragmentation Studies... 

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