Cyclopentanone Ring Expansion Leading to Functionalized δ-Lactams: Short Synthesis of Simple Sedum Alkaloids^†

Monosubstituted epoxides react with (cyclopentenyloxy)trimethylsilane to afford, after subsequent oxidative fragmentation, a pair of diastereomeric 8-membered iodolactones. When these lactones are separately treated with sodium azide, followed by reduction over Lindlar's catalyst, lactone ring contraction yields 6-membered monosubstituted lactams. When (R)-1,2-epoxypentane is used in this 5 + 3 − 2 overall ring expansion sequence, one final step involving δ-lactam to piperidine reduction yields natural (−)-halosaline and (−)-epihalosaline in five steps and 12% and 23% overall yields, respectively.