Diastereoselective 6-exo Radical Cyclizations of Oxime Ethers:  Total Synthesis of 7-Deoxypancratistatin

The development of an approach leading to the total synthesis of 7-deoxypancratistatin is described. The key features of the approach include a 6- exo radical cyclization reaction between a benzylic radical and an O -benzyloxime ether to establish the C 4a −C 10b bond. The stereochemistry of this reaction was examined in both acyclic radical precursors and ones in which the aryl moiety was tethered to the C 1 oxygen substituent. It was found that the use of such a tether was essential to obtain the stereochemical result required for the synthesis. The correct absolute and relative configurations at the hydroxylated carbons C 1 −C 4 were obtained using d -gulonolactone as the source of C 10b −C 4a .