First intermolecular regiospecific palladium-catalyzed enyne-diyne [4+2] cross-benzannulation reaction
First intermolecular regiospecific palladium-catalyzed enyne-diyne [4+2] cross-benzannulation reaction
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DOI：
10.1021/ja971935r
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发表时间：
1997-11-19
影响因子：
15
通讯作者：
Yamamoto, Y
中科院分区：
文献类型：
--
作者：
Gevorgyan, V;Takeda, A;Yamamoto, Y
自从1866年Berthelot报道了最早的乙炔热三聚化成苯的例子1，以及1948年Reppe证明了该反应的第一个过渡金属催化版本2以来，许多研究小组对乙炔的[2+ 2+ 2]环加成进行了广泛的研究，并在三十年前成为一个广阔的领域。大量的过渡金属催化剂，以及齐格勒型催化剂都能引起该反应。虽然这种方法成为组装苯环最有效的方法之一，但它存在严重的化学和区域选择性问题，通常会导致复杂的产物混合物，从而严重限制了该反应的合成效用（公式1）。Vollhardt成功地解决了几种分子内或部分分子内环三聚化模式的这些问题。在钴的催化作用下形成了三个新的键，以化学和区域选择性的方式生成环番型芳烃产物。6,7最近报道了两种互补的在钯催化下构建苯骨架的分子间方法：通过末端二炔的环三聚化合成1,3,5 -不对称苯1和通过共轭烯的[4+ 2]同二聚化合成1,4 -二取代苯2。9我们现在报告了分子间炔-二炔[4+ 2]交叉苯环化反应的第一个例子：炔3与二炔4的反应在没有产生任何区域异构体6的情况下，以高产量提供区域选择性1,2,4 -三取代苯5 （eq 2）。乙炔定位的各种不同的方式,解决装配一个中间我有三个新债券形成以来[2 + 2 + 2]cyclotrimerization (eq 1)。4,这一点我们将在情况共轭enyne 3与炔烃反应[4 + 2]环加成反应,这个反应10可以更特定选择的[2 + 2 + 2]环加成作用方式,因为只有两个债券形成的区域选择性仍让人怀疑。在[4+ 2]环加成反应中，我们尝试了一些炔作为炔的伙伴，发现共轭双炔4与3发生了区域特异性的交叉环加成反应。2-甲基-1-丁烯-3-炔（3a）与十二- 5,7 -二炔（4a）在5 mol% Pd (PPh3) 4的存在下，在THF中反应得到5a13，产率为89%（表1第1项）。通过对粗反应混合物的NMR和毛细管GLC分析，没有检测到6的痕迹。炔3b、炔c的烯-二炔交环反应似乎比相应的炔-炔同二聚反应快得多，因此等量的己基-(3b)和苄基-(3c)与4a、b不仅在区域-反应，而且在化学选择性反应中产生了排他的交环产物5d-f（表4-6）。相比之下，需要2-5倍的挥发性和低反应性3a（向diynes 4）的过量才能驱动反应完全转化为4（条目1-3）。16体积较大的炔4c与炔的反应速度比4a， b慢，因此采用缓慢添加炔3a， c以避免其二聚化（条目3和7）。很明显，区域特异性双键形成的事实
Since the earliest example of thermal trimerization of acetylene to benzene reported by Berthelot in 1866, 1 and the first transition-metal-catalyzed version of this reaction demonstrated by Reppe in 1948, 2 the [2+ 2+ 2] cycloaddition of acetylenes was extensively studied by number of research groups and became a vast field three decades ago. A large number of transition metal catalysts, as well as Ziegler-type catalysts, 3 give rise to this reaction. 4 Although this approach becomes one of the most powerful methods to assemble a benzene ring, it suffers from serious chemo-and regioselectivity problems which normally lead to complex mixtures of products, thus severely limiting the synthetic utility of this reaction (eq 1). 5 Vollhardt succeeded to solve these problems for several types of intramolecular 6 or partially intramolecular7 modes of cyclotrimerization: three new bonds were formed under the cobalt catalysis affording cyclophane-type aromatic products in chemo-and regioselective manner. 6, 7 Two complementary regiospecific intermolecular methods for constructing benzene skeleton under palladium catalysis were reported recently: the formation of 1, 3, 5-unsymmetrical benzenes 1 Via cyclotrimerization of terminal diynes8 and the synthesis of 1, 4-disubstituted benzenes 2 Via [4+ 2] homo-dimerization of conjugated enynes. 9 We now report the first example of intermolecular enyne-diyne [4+ 2] cross-benzannulation reaction: the reaction of enynes 3 with diynes 4 affording regioselectively 1, 2, 4-trisubstituted benzenes 5 in high to quantitative yields with none of the regioisomers 6 being produced (eq 2).Various different ways of the orientation of acetylenes are possible for assembling an intermediate i, since three new bonds are formed in [2+ 2+ 2] cyclotrimerization (eq 1). 4 It occurred to us that in the case where a conjugated enyne 3 would react with alkyne in a [4+ 2] cycloaddition manner, 10 this reaction could be more regioselective than the [2+ 2+ 2] mode of cycloaddition since only the regioselectivity of two bond formation remains questionable. After trying a number of alkynes in a role of enyne partner in the [4+ 2] cycloaddition, we discovered that conjugated diynes 4 underwent regiospecific cross-cycloaddition with 3. The reaction of 2-methyl-1-buten-3-yne (3a) with dodeca-5, 7-diyne (4a) in the presence of 5 mol% Pd (PPh3) 4 in THF gave 5a13 in 89% yield (entry 1, Table 1). No traces of 6 were detected by NMR and capillary GLC analyses of crude reaction mixtures. The enyne-diyne crossannulation reaction of enynes 3b, c appeared to be much faster than the corresponding enyne-enyne homo-dimerization, 14 thus an equimolar amount of hexyl-(3b) and benzyl-(3c) enyne reacted with 4a, b not only in regio-, but also in chemoselective manner affording the cross-annulation products 5d-f, exclusively (entries 4-6). In contrast, a 2-5-fold excess of volatile and less-reactive 3a (toward diynes 4) was needed to drive the reaction to complete conversion of 4 (entries 1-3). 16 Bulky diyne 4c reacted with enynes rather slower than 4a, b, thus the slow addition of the enynes 3a, c was employed in order to avoid its dimerization (entries 3 and 7). Apparently, the fact of regiospecific two bonds formation