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

Article abstract of DOI:10.1021/jo00129a025

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 (<2percent) and the instability of several key intermediates; these deficiencies were rectified in a second-generation approach that produced optically active material (18 steps from 19a, 2.1percent overall).The successful strategies exploited enolate generation via either conjugate additions to α,β-enones or the Evans oxy-Cope rearrangement as key regiochemical control elements.