Yang W, Drueckhammer D G
Department of Chemistry, State University at Stony Brook, Stony Brook, New York 11794-3400, USA.
J Am Chem Soc. 2001 Nov 7;123(44):11004-9. doi: 10.1021/ja010726a.
Computational studies were performed in an effort to understand the relative reactivity of oxoesters and thioesters in nucleophilic acyl transfer reactions. Transition state models were developed for the reactions of methyl acetate and methyl thioacetate with hydroxide, ammonia, and methylcyanoacetate carbanion. Quantum mechanical calculations based on these models reproduced experimental observations that oxoesters and thioesters have similar reactivity toward hydroxide while thioesters are about 100-fold and at least 2000-fold more reactive than oxoesters toward amine and carbanion nucleophiles, respectively. NBO analysis was performed to elucidate the role of electron delocalization in reactant and transition state stabilization. These calculations indicate similar losses of delocalization energy for the oxoester and thioester in going from the reactants to the transition state in reaction with hydroxide while the loss of delocalization energy is significantly greater for the oxoester in reactions with the other nucleophiles. Bond rotational analysis of the transition states for the reactions with hydroxide and ammonia provide support for an important role of the p(X) --> sigma(C-Nu) interaction (X = O or S of the oxoester or thioester respectively, Nu = nucleophile) in governing the reactivity of oxoesters and thioesters in nucleophilic acyl substitution.
为了理解氧酯和硫酯在亲核酰基转移反应中的相对反应活性，进行了计算研究。针对乙酸甲酯和硫代乙酸甲酯与氢氧化物、氨和氰基乙酸甲酯碳负离子的反应，建立了过渡态模型。基于这些模型的量子力学计算重现了实验观察结果：氧酯和硫酯对氢氧化物具有相似的反应活性，而硫酯对胺和亲核碳负离子的反应活性分别比氧酯高约100倍和至少2000倍。进行了自然键轨道（NBO）分析，以阐明电子离域在反应物和过渡态稳定化中的作用。这些计算表明，在与氢氧化物反应时，从反应物到过渡态，氧酯和硫酯的离域能损失相似，而在与其他亲核试剂反应时，氧酯的离域能损失明显更大。对与氢氧化物和氨反应的过渡态进行键旋转分析，为p(X)→σ(C-Nu)相互作用（X分别为氧酯或硫酯的O或S，Nu为亲核试剂）在决定氧酯和硫酯在亲核酰基取代反应中的反应活性方面的重要作用提供了支持。
