Tremorgenic Indole Alkaloids. 9. Asymmetric Construction of an Advanced F-G-H-Ring Lactone Precursor for the Synthesis of Penitrem D

Lactone (+)-12 is envisioned as the precursor to the F—G—H rings of penitrem D (4) in our ongoing synthetic venture. The efficient, stereocontrolled introduction of the vicinal quaternary methyl groups present the major challenge in the construction of this subunit. Our first route to (±)-12 was marked by low overall yield (<2%) and the instability of several key intermediates; these deficiencies weee rectified in a second-generation approach that produced optically active material (18 steps from 19a, 2.1% overall). The successful strategies exploited enolate generation via either conjugate additions to αpha;,β-enones or the Evans oxy-Cope rearrangement as key regiochemical control elements.