Free-Energy Surfaces for Liquid-Phase Reactions and Their Use To Study the Border Between Concerted and Nonconcerted α,β-Elimination Reactions of Esters and Thioesters
Free-Energy Surfaces for Liquid-Phase Reactions and Their Use To Study the Border Between Concerted and Nonconcerted α,β-Elimination Reactions of Esters and Thioesters
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DOI：
10.1021/ja101104q
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发表时间：
2010-08-18
影响因子：
15
通讯作者：
Truhlar, Donald G.
中科院分区：
文献类型：
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作者：
Kim, Yongho;Mohrig, Jerry R.;Truhlar, Donald G.
在实验上很难区分β-消除的协同二级机理和具有离散碳负离子中间体的非协同机理，但量子化学在液体溶液中找到自由能表面的固定点的能力，甚至对于复杂的试剂，为阐明这种机理提供了一个新的工具。在这里，我们用液相密度泛函理论计算了四个碱基引发的乙酰氧基酯和甲氧基酯及其类似的硫代酯的α，β消除反应的过渡态和中间体。这些结构的几何构型、自由能和电荷分布支持与乙酰氧基酯3、乙酰氧基硫酯4和甲氧基硫酯6的共轭碱(E1cB(I))机制的逐步不可逆一级消除。而甲氧基酯5具有良好的亲核能力和较弱的酸性质子，遵循协同但不同步的E2机制，具有类E1cB的过渡态。反过渡态比正过渡态更有利，即使对于较差的亲核性和较酸性的硫代酯也是如此。这篇文章包括了一个用自由能表面描述液相反应的一般方案。
Distinguishing between the concerted second-order mechanism for beta-eliminations and nonconcerted mechanisms with discrete carbanion intermediates is very difficult experimentally, but the ability of quantum chemistry to find stationary points of the free-energy surface in liquid-phase solutions, even for complex reagents, provides a new tool for elucidating such mechanisms. Here we use liquid-phase density functional theory calculations to find transition states and intermediates on the free-energy surfaces of four base-initiated alpha,beta-eliminations of acetoxy and mesyloxy esters and their analogous thioesters. The geometries, free energies, and charge distributions of these structures support a stepwise irreversible first-order elimination from a conjugate base (E1cB(I)) mechanism with acetoxy ester 3, acetoxy thioester 4, and mesyloxy thioester 6. However, mesyloxy ester 5, which has an excellent nucleofuge and a less-acidic proton, follows a concerted but asynchronous E2 mechanism with an E1cB-like transition state. The anti transition state is more favorable than the syn one, even for the poorer nucleofuge and more-acidic thioesters. The article includes a general scheme for describing liquid-phase reactions in terms of free-energy surfaces.