|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 2000 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1999 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1998 : ¥1,800,000 (Direct Cost : ¥1,800,000)
Recently, we have developed a new type of coupling reagent that allows participation of secondary allylic esters as substrates, thus indicating a high reactivity of the reagents. In this project, we have investigated coupling reaction of these reagents and substrates which have not been investigated due to steric hinderance, and the fruitful results are presented below.
(1) Coupling reaction of 8-acetoxy-octalone-Δ^<1(9)>-2 and phenylborates in the presence of a nickel catalyst proceeded stereo- and regioselectively to afford 8-phenyloctalone-Δ^<1(9)>-2 in good yield. Interestingly, the observed stereochemistry is independent of that of the starting allylic substrate. This outcome is not consistent with the well-established mechanism, and we are proposing another one in which the nickel enolates play a central role.
(2) Coupling reaction of cyclohexenyl acetates proceeds through the π-allylnickel species which possesses a symmetrical plane and hence presence of a chiral center in a reage
nt is expected to provide a bias for the regioselectivity. This possibility was examined with arylborates with a chiral substituent at the ortho position to result in a production of one diastereomer highly selectively.
(3) Although cis 1-bromoalkenes with a silyloxy substituent at 3-position is less reactive substrates toward the coupling reaction due to the steric hindrance, alkenylborates was found to furnish coupling products efficiently. The reaction was successfully applied in a total synthesis of 10,11-dihydroleukotriene B_4 and the related molecules.
(4) With the above reaction, determination of the stereochemistry of natural korormicin was investigated. In practice, possible four diastereoisomers were synthesized stereoselectively by using this coupling reaction, and comparison of their specific rotations with that of the natural one revealed that the (5S,3'R,9'S,10'R)-isomer is unambiguously to be the natural korormicin.
(5) Aldol reaction at the α dash position of γ-alkeny-α, β-unsaturated cyclopentenones, easily prepared from the coupling product of 4-cyclopentene-1,3-diol and borates, is investigated and applied to synthesis of Δ^7-PGA_1 methy ester. Less