Coupling Reaction of Highly Reactive Borates and Substrates with sterichindrance

高反应性硼酸盐与底物的偶联反应

基本信息

批准号：
10650843
负责人：
KOBAYASHI Yuichi
金额：
$ 2.05万
依托单位：
Tokyo Institute of Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

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

最近，我们开发了一种新型偶联剂，它允许仲烯丙酯作为底物参与，从而表明该试剂具有高反应活性。在这个项目中，我们研究了这些试剂与底物的偶联反应，而这些反应尚未被研究。 (1)8-乙酰氧基-辛酮-Δ^<1(9)>-2与苯基硼酸酯在存在下的偶联反应镍催化剂进行立体选择性和区域选择性地以良好的收率提供 8-苯基辛酮-Δ^<1(9)>-2，所观察到的立体化学与起始烯丙基底物的立体化学无关。已建立的机制，我们提出了另一种以烯醇镍起核心作用的机制。（2）乙酸环己烯酯的偶联反应通过π-烯丙基镍物种具有对称平面，因此在区域中存在手性中心，预计会为区域选择性提供偏差，我们用邻位具有手性取代基的芳基硼酸盐检验了这种可能性，从而产生了高选择性地生产一种非对映异构体。(3) 尽管 3 位具有甲硅烷氧基取代基的顺式 1-溴代烯烃是反应性较低的底物由于空间位阻，烯基硼酸酯可以有效地促进偶联反应，该反应成功地应用于10,11-二氢白三烯B_4及相关分子的全合成。(4)通过上述反应，测定了在实践中，研究了天然科罗米星的立体化学，利用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，并比较了它们的比旋光度。天然异构体表明(5S,3'R,9'S,10'R)-异构体明确是天然的科罗米星。(5)γ-烯基-α,β-不饱和环戊烯酮的α破折号位置的羟醛反应，很容易由 4-cyclopentene-1,3-diol 和硼酸盐的偶联产物制备，并被研究并应用于 Δ^7-PGA_1 甲基的合成酯少。