Xanthates, free-radical reduction

A relevant reductive process, which has found wide application in organic synthesis, is the deoxygenation of alcohols introduced in 1975 by Barton and McCombie [58]. Reaction (4.28) shows that the thiocarbonyl derivatives, easily obtained from the corresponding alcohol, can be reduced in the presence of BusSnH under free radical conditions. The reactivity of xanthates and thiocarbonyl imidazolides [58] was successfully extended to 0-arylthiocarbonates [59] and (9-thioxocarbamates [60]. Several reviews have appeared on this subject, thus providing an exhaustive view of this methodology and its application in natural product synthesis [61-64]. 

Cyclic enol ethers such as 8 are also easily epoxidized. R. Daniel Little of the University of California, Santa Barbara has found (J. Org. Chem. 2005, 70, 5249) that such an epoxide is reduced with Tifffl) regioselectively to the radical, that adds with remarkable diastereocontrol to enones such as 7 to give the adduct 9. Reductive cyclization converted 9 to the tricyclic ether 10. The C-Br bond of 10 was stable both to the Et,SiH conditions, and to the free radical removal of the xanthate derived from the alcohol. 

A Beckmann rearrangement-reduction sequence has been used to access a number of substituted H- 1-benzazepine derivatives, with the required substituted a-tetralone precursors being prepared by a xanthate-based free radical cyclization process <2006BMC6165>. 

Reductive radical elimination (Barton deoxygenation) of the 3, 4 -xanthate derivative of neamine (70) has been used to prepare the key intermediate 71 (compounds 70, 71) for the synthesis of the 3, 4 -dideoxyneamine analog gentamine Cia [52]. In this synthesis, a precursor possessing free hydroxyl groups at positions 3 and 4 was treated with a mixture of carbon disulfide, aqueous sodium hydroxide, and methyl iodide in DMSO to afford compound 70. Subsequent reduction of 70 with tributyltin hydride furnished the olefin 71, which affer cafalyfic hydrogenation and deprofecfion was converted to gentamine Cia. 

---