Vk. Aggarwal et al., SCOPE AND LIMITATIONS IN PALLADIUM-CATALYZED SUBSTITUTION-REACTIONS OF UNSATURATED FUSED LACTONES, Journal of organic chemistry, 62(14), 1997, pp. 4665-4671
The palladium-catalyzed nucleophilic substitution of C-4-substituted 2
-oxabicyclo[3.3.0]oct-7-en-3-ones (unsaturated, fused lactones) have b
een studied particularly in relation to how electronic and steric fact
ors influenced the rate and efficiency of substitution reactions. Thus
, a range of a-substituted lactones were prepared (X = H, Me, OH, OAc,
Br, N-3, NHCBZ) and subjected to palladium-catalyzed substitution rea
ction with diethyl sodiomalonate, and it was found that reaction rates
increased with increasing electron-withdrawing ability of the substit
uent and that there was a strong correlation between rate and pK(a) of
the corresponding substituted acetic acids (XCH2-CO2H). The only exce
ption to the correlation was with X = OH, in which case the endo isome
r reacted considerably faster than expected and the exo isomer reacted
much slower than expected. It was also found that the rates of reacti
on of the endo isomers were greater than the exo isomers. The increase
d rates have been accounted for by a shift in equilibrium between the
lactone and the pi-allyl palladium intermediate toward the latter spec
ies due to the increased stability of the carboxylate (electronic effe
cts) or relief of steric hindrance in the starting lactone. The scope
and limitations of the palladium-catalyzed substitution reaction were
studied by reacting a range of lactones with a range of nucleophiles.
Lactones with unactivated leaving groups such as 2 (X = H) coupled eff
iciently with good nucleophiles such as malonate but only poorly with
less reactive nucleophiles such as azide. Lactones with activated leav
ing groups such as 4a (X = OH) coupled efficiently with a broad range
of nucleophiles.