Enantioselective Synthesis of (R)‐(+)‐Pulvilloric Acid

Abstract

AbstractThe fungal metabolite (R)‐(+)‐pulvilloric acid [(+)‐1] was synthesized for the first time. Reaction of the Grignard reagent of 5 with 2‐pentyloxirane (S)‐(−)‐4 in the presence of 1,5‐cyclooctadienecopper(I) chloride as the catalyst led to (S)‐(+)‐6. The enantiomer (S)‐(−)‐4 was prepared from dimethyl L‐malate via the dioxolane (S)‐(+)‐3. The alcohol (S)‐(+)‐6 was transformed into (R)‐(−)‐6 via the benzoate (R)‐(−)‐7 by a Mitsunobu reaction. Hydrogenolysis of (−)‐6 gave the resorcyl alcohol (R)‐(+)‐2. The remaining steps to produce (R)‐(+)‐1 from (+)‐2 required carboxylation to (R)‐(−)‐8, formylation and in situ ring closure with triethyl orthoformate to furnish the required quinomethide structure. Application of the same reactions to (S)‐(+)‐6 afforded (S)‐(−)‐1 via the intermediates (S)‐(−)‐2 and (S)‐(+)‐8. With (±)‐6 as starting material (±)‐2, (±)‐8 and (±)‐1 were prepared.