Electronic control of the Bergman cyclization: The remarkable role of vinyl substitution
Electronic control of the Bergman cyclization: The remarkable role of vinyl substitution
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DOI：
10.1021/ja0033032
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发表时间：
2001-03-14
影响因子：
15
通讯作者：
Warner, PM
中科院分区：
文献类型：
--
作者：
Jones, GB;Warner, PM
本文报道了乙烯基取代对3-烯-1，5-二炔环芳构化反应（Bergman环化反应）影响的从头算研究。大部分的计算都是使用BLYP版本的密度泛函理论进行的，一些关键化合物使用了更高水平的Brueckner轨道计算。总共研究了46种烯二炔，44种环化过渡态，39种单重态对苯炔和28种相关的三重态对苯炔，包括简单的乙烯基取代和环状的例子。数据表明，强吸电子基团增加环化势垒，而a-供电子基团降低它;它的共轭，特别是捐赠，几乎没有影响。大多数环化，包括涉及杂芳环的环化，都会稍微增强屏障（6 MR）或稍微提高屏障（5 MR）。对于较小的环或带电环，可以看到较大的影响。一些先前观察到的明显的速率抑制被认为是由于可逆性或正向反应的中间体对-苯炔，从而抑制从H提取步骤，完成环芳构化。H提取反应，从对苯炔单重态-三重态能隙和等键方程判断，也检查。预测了一些杂芳族系统的意外行为。最后，我们预计如何将这些结果可能被应用到后续的生物应用的前药候选人的设计。
We report an ab initio study of the effect of vinyl substitution on the cycloaromatization of 3-ene-1,5-diynes (the Bergman cyclization). The majority of the calculations were conducted by using the BLYP version of Density Functional Theory, and higher level Brueckner orbital calculations were used for a few key compounds. In all, 46 enediynes, 44 cyclization transition states, 39 singlet p-benzynes, and 28 related triplet p-benzynes were studied, including simple vinyl-substituted and annulated examples. The data indicate that strongly electron-withdrawing groups increase the cyclization barrier, while a-donating groups decrease it; it conjugation, especially donation, has little effect. Most annulations, including those involving heteroaromatic rings, Power the barrier slightly (6 MR) or raise it slightly (5 MR). Larger effects are seen for smaller rings or charged rings. Some previously observed apparent rate inhibitions are seen to be due to reversibility or forward reactivity of the intermediate p-benzynes, which are thereby inhibited from the H abstraction step that completes cycloaromatization. H abstraction reactivity, as judged from the p-benzyne singlet-triplet energy gap and from isodesmic equations, is also examined. Unexpected behavior is predicted for some heteroaromatic systems. Finally, we anticipate how these results may be applied to the design of prodrug candidates for subsequent biological application.