Department of Chemistry, Indian Institute of Technology Kharagpur , Kharagpur 721 302, India.
J Org Chem. 2016 Sep 2;81(17):7411-8. doi: 10.1021/acs.joc.6b01053. Epub 2016 Aug 8.
We studied the variation in mechanism among different bispropargyl substrates-sulfone, sulfide, ether, amine, and methane-toward Garratt-Braverman (GB) cyclization using density functional theory calculations. Isomerization and cycloaddition are the key steps in the GB cyclization. To compare the reactivity among the various substrates, we computed the free energy of activation (ΔG(⧧)) for the cycloaddition and the cyclization steps, whereas we used the theoretically computed pKa values for the isomerization steps. Our results suggest that the sulfones undergo a relatively fast isomerization followed by slower cyclization, while the ethers undergo a slow isomerization followed by easy cyclization. The methanes and amines are similar to the ethers, and the sulfides showed intermediate behavior. We extended our study to unsymmetrical substrates and compare the results with experiments that suggest the isomerization to be the rate-limiting step for bispropargyl ethers, while cyclization through a diradical intermediate is crucial to the rate for the bispropargyl sulfones. On the basis of these findings, we made predictions on the selectivity of unsymmetrical bispropargyl sulfones, amines, methanes, and sulfides. This is the first detailed mechanistic study on the GB cyclization of bispropargyl substrates other than sulfones.
我们使用密度泛函理论计算研究了不同的双炔丙基底物（砜、硫醚、醚、胺和甲烷）向 Garratt-Braverman（GB）环化的机理变化。异构化和环加成是 GB 环化的关键步骤。为了比较各种底物的反应性，我们计算了环加成和环化步骤的自由能活化（ΔG(⧧)），而对于异构化步骤，我们使用理论计算的 pKa 值。我们的结果表明，砜经历相对较快的异构化，随后是较慢的环化，而醚经历较慢的异构化，随后是容易的环化。甲烷和胺类似于醚，而硫醚表现出中间行为。我们将研究扩展到非对称底物，并将结果与实验进行比较，实验表明异构化是双炔丙基醚的限速步骤，而通过自由基中间体的环化对双炔丙基砜的速率至关重要。基于这些发现，我们对非对称双炔丙基砜、胺、甲烷和硫醚的选择性进行了预测。这是对除砜以外的双炔丙基底物的 GB 环化的首次详细的机理研究。
