Displacement of bridgehead sulfonate esters with organometallic reagents: synthesis of 13-alkylated gibberellins

Gibberellin A3 is converted to 13-methyl GA4 in nine steps and 58% overall yield. A key step in the synthesis is the substitution of a bridgehead sulfonate ester by an alkyl group. A series of organometallic reagents have been investigated to effect this transformation; optimal yields are obtained from reaction of a methanesulfonate with a Gilman-type organocuprate in diethyl ether, in the presence of boron trifluoride–diethyl ether, thus enabling a variety of bridgehead substituents to be introduced in good to excellent yield.