Coupling Reaction of Highly Reactive Borates and Substrates with sterichindrance

最近，我们已经开发了一种新型的偶联试剂，它允许作为底物的仲烯丙基酯的参与，从而表明该试剂的高反应性。在本项目中，我们研究了这些试剂与底物的偶联反应，这些反应由于空间位阻而没有被研究过，并取得了丰硕的成果。(1)8-乙酰氧基辛甲酮-Δ^<1（9）>-2与苯硼酸酯在镍催化剂存在下进行立体选择性和区域选择性偶联反应，得到8-苯基辛甲酮-Δ^<1（9）>-2。有趣的是，观察到的立体化学是独立的起始烯丙基底物。这一结果是不符合既定的机制，我们提出了另一个镍烯醇化物发挥核心作用。(2)乙酸环己烯酯的偶联反应通过π-烯丙基镍物种进行，该物种具有对称平面，因此在区域中存在手性中心 关于我们 预期NT提供区域选择性的偏差。用在邻位具有手性取代基的芳基硼酸酯检查这种可能性，以导致高度选择性地产生一种非对映体。(3)虽然顺式1-溴代烯烃与甲硅烷基氧基取代基在3-位是对偶联反应的反应性较低的底物，由于空间位阻，烯基硼酸酯被发现有效地提供偶联产物。该反应已成功地应用于10，11-二氢白三烯B_4及其相关分子的全合成。(4)利用上述反应，对天然科罗米星的立体化学进行了研究。在实际应用中，通过该偶联反应立体选择性地合成了可能的四种非对映异构体，并将它们的比旋光度与天然产物的比旋光度进行了比较，结果表明，（5S，3 'R，9'S，10' R）-异构体无疑是天然的科罗米星。(5)研究了由4-环戊烯-1，3-二醇与硼酸酯偶联产物容易制备的γ-烯基-α，β-不饱和环戊烯酮的α-位Aldol反应，并将其应用于Δ^7-PGA_1甲酯的合成。少

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 … More 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