Diastereoselective 6-exo radical cyclizations of oxime ethers:: Total synthesis of 7-deoxypancaratistatin

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.