Synthesis and Reactivity of a p-Methoxyphenyl-Substituted Enediyne. A Case of Electronic Influence on the Rate of the Bergman Cycloaromatization

Bicyclo[7.3.1]diynes 19a and 19b were prepared by using dibromo olefin 11 and ketone 12 as building blocks. The key step of the synthetic sequence is an intramolecular Nicholas reaction of 17 to give the bicyclo[7.3.1]diyn‐10‐one dicobalthexacarbonyl adducts 18a and 18b (66% total yield). Oxidative decomplexation of 18a and 18b with cer(IV) ammonium nitrate gave the diynes 19a and 19b, respectively. Both diynes 19a and 19b could be oxidatively converted into the enediyne 20 by using DDQ. In contrast to the unsubstituted enediyne 4, compound 20 can be isolated at room temperature Quantitative kinetic measurements of the rate of the Bergman cyclization of 20 gave ΔG# (37°C) = 111 kJ mol−1. This value is 12.3 kJ mol−1 higher than that of 4. The difference in the free activation energy between 20 and 4 is attributed to electronic effects.