Development of Highly Slective Reactions Using Allylic Barium Reagents

较重的碱土金属的有机金属化合物在有机合成中几乎没有应用，因为它们与格氏试剂相比没有任何优势。我们一直对使用钡或锶试剂感兴趣，期望这些物质表现出与普通镁试剂明显不同的立体化学稳定性。我们已经报道了原位生成的反应性钡和烯丙基氯化物可以很容易地制备烯丙基钡试剂，并与各种羰基化合物在78℃下反应生成具有很高α选择性和起始氯化物构型保留的均烯丙基醇。在这项研究中，我们进一步研究了烯丙基钡试剂与其他亲电试剂的反应，从而发现了与烯丙基卤化物、环氧化物和亚胺的高度选择性的烯丙基化反应。值得注意的是，醛胺通过烯丙基钡试剂转化为均烯丙基胺，其中通过简单地改变反应温度可以选择性地获得α和γ加合物。二（2,2,2-三氟乙基）磷酸是烯丙醇衍生物与烯丙基钡试剂选择性交叉偶联反应的优越离去基。利用该离去基还实现了选择性barbier型交叉偶联反应。例如，当(E) -2-辛烯基- 1-双（2,2,2-三氟乙基）磷酸盐和(E) -2-十烯基氯的1:1混合物用1等量的活性钡处理时，得到的交叉偶联产物选择性为86%，α, α′/ α， α′比为94:6。在实际应用中，还研究了烯丙基钡试剂的大规模羧化反应，在7 mmol的反应中，产物的收率不断达到70%以上。

The organomatallic compounds of heavier alkaline earth metals have found little application in organic synthesis, since they do not offer any advantages over Grignard reagents. We have been interested in using barium or strontium reagents with the anticipation that such species should exhibit markedly different stereochemical stability from that the ordinary magnesium reagent. We have already reported that the allylic barium reagents can be easily prepared from in situ generated reactive barium and allylic chlorides, and react with a variety of carbonyl compounds at-78ﾟC to produce the homoallylic alchols with remarkably high alpha-selectivity and retention of the configuration of the starting chloraide.In this research, we further examined the reactions of allylic barium reagents with other electrophiles and thus highly alpha-selective allylation reactions with allylic halides, epoxides, and imines were found. Noteworthy was the fact that aldimines were transformed into homoallylic amines by treatment with allylic barium reagents in which both the alpha-and gamma-adducts were selectively obtained by simply changing the reaction temperature. Bis(2,2,2-trifluoroethyl)phoshate was found to be a superior leaving group for alpha, alpha'-selective cross-coupling reaction of allylic alcohol derivatives with allylic barium reagents. Selective Barbier-type cross-coupling reation was also achieved using this leaving group. For example, when a 1 : 1 mixture of (E) -2-octenyl 1-bis (2,2,2-trifluoroethyl) phosphate and (E) -2-decenyl chloride was teated with 1 equiv of reactive barium, the cross-coupling products were obtained with 86% selectivity and an alpha, alpha'/alpha, gamma' ratio of 94 : 6 . For practical use, largescale carboxylation of an allylic barium reagent was also investigated and over 70% yield of the product was constantly obtained in the 7 mmol-scale reaction.