Thermolysis of 1,3,8-nonatriyne: Evidence for intramolecular [2+4] cycloaromatization to a benzyne intermediate
Thermolysis of 1,3,8-nonatriyne: Evidence for intramolecular [2+4] cycloaromatization to a benzyne intermediate
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DOI：
10.1021/ja972141f
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发表时间：
1997-10-15
影响因子：
15
通讯作者：
Johnson, RP
中科院分区：
文献类型：
--
作者：
Bradley, AZ;Johnson, RP
环芳香化反应由于其在抗肿瘤药物化学中的潜在作用而引起了人们的极大兴趣。1原则上，芳环也可以通过二炔+炔环加成反应直接制备，如式1所示，生成邻苯。这个概念上简单的过程是已知的炔+烯烃，炔+炔和二炔+烯烃环加成的逻辑延伸（公式2-4），这些环加成已经在物质中得到证明，其中反应组分由三碳系链结合在一起。2,3在闪蒸真空热解实验中，可预测的二次过程的观察结果支持了应变循环累积的中介作用。本文描述了1,3 -二炔+炔[2+ 4]环芳构化（eq 1）作为Diels-Alder型环加成新模式的实验证据。虽然这个过程在几何上似乎是不可能的，从头计算研究支持母体双炔+炔环加成步骤的可行性。5 1,3,8 -壬atriyne(5)的制备步骤如方案1所示。1,4 -二（三甲基硅基）丁二炔的烷基化和随后的TMS去除使总收率达到50%。在580℃的石英仪器中，在10-2 Torr下对纯5进行闪蒸真空热裂解，干净地产生了两种产品，通过与真实样品的比较，鉴定出这两种产品分别为indan（7.86%）和indee（8.14%）。这些占产品的95%左右，没有原料残留。在这种热解过程中也形成了一些烟尘，但没有证据表明存在预期的苯6二聚体。650℃时，产物比为60:40，表明茚二酮主要是茚二酮脱氢的二次产物。这是有文献先例的，并在相同条件下通过对印度的热解得到了证实。得到所观察到的产物最直接的途径是通过分子内[2+ 4]环加成得到苯衍生物6。在类似的热解反应条件下，苯的还原已有充分的先例。7然而，热1,2 -移位是众所周知的炔；另一种机制（方案2）将通过偏乙烯基11。CH键插入和Bergman环化1,8可能得到对苯13，从而得到吲哚。9烯二炔12是未知的，尽管已经研究了更大的环同源物。为了区分这两种路径，我们制备并热解了5-d2。分离产物的1H NMR谱清晰地显示了芳香族氢的AB自旋体系；这些结果符合结构10和[2+ 4]环加成机理。从这些反应中分离出的独立分子中也观察到类似的氘标记。用从头算法估计了双炔加炔环加成的几何和能量可行性。静定点定位于MP2 (FC)/6-31G*水平，然后进行解析Hessian计算和单点MP4SDTQ/6-31G*能量评价。这个水平的理论正确地描述了母体Diels-Alder反应的能量学，精确到几千卡/摩尔。13过渡态预测为C2V对称，初生CC键距离为2.196 Å；这与其它周环过渡态的几何形状很好地吻合。14预言者
Cycloaromatizations have been of intense recent interest because of their potential involvement in the chemistry of antitumor agents. 1 In principle, aromatic rings might also be prepared directly by diyne+ alkyne cycloaddition reactions, as exemplified by eq 1, which yields o-benzyne. This conceptually simple process is a logical extension of known enyne+ alkene, enyne+ alkyne, and diyne+ alkene cycloadditions (eqs 2-4) which have been previously demonstrated in substances where the reacting components are held together by a threecarbon tether. 2, 3 In flash vacuum thermolysis experiments, the intermediacy of strained cyclic cumulenes4 was supported by the observation of predictable secondary processes. We describe here experimental evidence for 1, 3-diyne+ alkyne [2+ 4] cycloaromatization (eq 1) as a new mode of Diels-Alder type cycloaddition. Although this process might seem geometrically improbable, ab initio computational studies support the feasibility of the parent diyne+ alkyne cycloaddition step. 5 1, 3, 8-Nonatriyne (5) was prepared in several steps as shown in Scheme 1. Alkylation of 1, 4-bis (trimethylsilyl) butadiyne and subsequent TMS removal gave 5 in 50% overall yield. Flash vacuum thermolysis of pure 5 at 10-2 Torr in a quartz apparatus at 580 C cleanly yielded two products, which were identified by comparison to authentic samples as indan (7, 86%) and indene (8, 14%). These accounted for> 95% of the products, and no starting material remained. Some soot also formed in this pyrolysis but there was no evidence for the expected dimers of benzyne 6. At 650 C, the product ratio was 60: 40, which suggests that indene is predominantly a secondary product of indan dehydrogenation. This has literature precedent6 and was confirmed by pyrolysis of indan under the same conditions. The most straightforward route to the observed product is through intramolecular [2+ 4] cycloaddition to give benzyne derivative 6. There is ample precedent for reduction of benzynes under similar pyrolytic reaction conditions. 7 However, thermal1, 2-shifts are well-known for alkynes; one alternative mechanism (Scheme 2) would pass through vinylidene 11. CH bond insertion and Bergman cyclization1, 8 might give p-benzyne 13 and, hence, indan. 9 Enediyne 12 is unknown, although larger ring homologues have been investigated. 10 To distinguish these two paths, we prepared and pyrolyzed 5-d2. The 1H NMR spectrum of the isolated indan cleanly showed an AB spin system for the aromatic hydrogens; these results are consistent with structure 10 and a [2+ 4] cycloaddition mechanism. Similar deuterium labeling was observed in the indene isolated from these reactions.Ab initio calculations were carried out to estimate the geometric and energetic feasibility of a diyne plus alkyne cycloaddition. Stationary points were located at the MP2 (FC)/6-31G* level, followed by analytic Hessian calculation and single-point MP4SDTQ/6-31G* energy evaluation. 11, 12 This level of theory correctly describes energetics of the parent Diels-Alder reaction to within a few kcal/mol. 13 The transition state is predicted to have C2V symmetry, with a nascent CC bond distance of 2.196 Å; this is in good agreement with geometries of other pericyclic transition states. 14 The predicted