Stereocontrol with Lithium Trimethylzincate toward Gibberellin Synthesis

Abstract

AbstractSubstrate control in target‐oriented synthesis is generally important in establishing the required stereogenic center rather than reagent control. During the course of the total synthesis toward Gibberellin A3 (1), a model compound (21) as the A‐ring of 1 was accomplished in five overall steps with an overall yield of 15 %, starting from furfural through conjugate addition of lithium trimethylzincate to oxabicyclo[2.2.1]heptadienedicarboxylic ester (2) as the key step. Relative to more common lithium dimethylcuprate or aluminum reagents, this zincate complex showed a complete selectivity with higher reactivity than with other simple enone compounds. The incoming methyl group was 100 % selective from the ring oxygen side of 2, and the enolate intermediate can be protonated stereoselectivly without the bridge‐oxygen‐ring opening.