The reaction of the dilithio derivative of dimethyl cis-4-cyclohexen-1,2-dicarboxylate with 3substituted propiolic acid phenyl esters proceeds via an unusual mechanistic path to generate fused bicyclic 2cyclopentenones in a single step.
The first total synthesis of a member of the gingkolide family, (f)-bilobalide (I),' has recently been realized using as a key intermediate bicyclic keto ester 2, which contains all of the carbon atoms required for the construction of 1.2 The synthesis of 2 can be accomplished in a single step starting from dimethyl &s-4cyclohexen-1,2-dicarboxylate by a highly useful new synthetic process which is detailed herein. These results substantially extend the annulation methodology described in a previous report.3
Dimethyl cis-4-cyclohexen-1,2-dicarboxylate was converted to the dilithio derivative 3 (2.2 equiv of LDA, 3 equiv of HMPA in THF at -78'C for 0.5 h and O'C for 0.25 h)3-5 and treated at -4YC with 1 equiv of phenyl3t-butylpropiolate.6
After 30 min at -45ยฐC and 2 h at 0ยฐC the reaction mixture was quenched by addition of acetic acid and the product was isolated by extraction (after removal of THF in vacua and addition of water) and sg column chromatography. Pure bicyclic keto ester 2 was obtained in 70% yield and was identical with material prepared from keto ester 53 by the sequence: (1) a-phenylselenation;
(2) oxidation with Hz02 and elimination;
(3) addition of di-t-butylcopperlithium;
(4) a-phenylselenation; and (5) oxidation with Hz02 and elimination.2 0 1 5241 8. This research was assisted financially by a grant from the National Science Foundation.