Predicting Reactivity and Stereoselectivity in the Nazarov Reaction: A Combined Computational and Experimental Study
Predicting Reactivity and Stereoselectivity in the Nazarov Reaction: A Combined Computational and Experimental Study
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DOI：
10.1002/chem.200801030
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发表时间：
2008-01-01
影响因子：
4.3
通讯作者：
Occhiato, Ernesto G.
中科院分区：
文献类型：
--
作者：
Cavalli, Andrea;Pacetti, Alessandro;Occhiato, Ernesto G.
通过实验和DFT计算，详细研究了由二烯酮或烷氧基三烯质子化产生的双阳离子的Nazarov反应。特别是，在B3 LYP/6- 311 G ** 水平的理论计算准确地预测，并占，布朗斯台德酸催化的4 π电子系统的电环化的结果，其中一个参与该过程的双键嵌入在N-和S-杂环。计算表明，这两个杂原子都能够通过稳定过渡态中在C-6（C-2）处产生的部分正电荷来加速环闭合，其中S-杂环衍生物比相应的含N化合物更具反应性。一般而言，通过烷氧基三烯的质子化产生的双阳离子预期比通过相应的二烯酮的质子化获得的那些反应更快，因为后者通过氢键稳定。杂环上取代基的存在仅在N-杂环衍生物的情况下显着影响立体选择性（反式选择性），其中2-烷基是轴向取向的，仅提供顺式-2，5-二取代的异构体。相反，与取代的S-杂环化合物，预期的torquosectivity是非常低的，事实上，一个3：1的非对映异构体之间的反式和顺式产品的混合物，实验发现闭环后。对于这项研究，适当的N-和S-含二烯酮和烷氧基三烯的合成被实现，以评估DFT计算的预测能力，这是非常好的，在所有的情况下检查，无论是在反应性和立体选择性方面。计算和实验结果之间的一致性，因此，在B3 LYP/6- 311 G ** 理论水平上的DFT计算的有用性作为一个强大的工具预测的反应性和立体选择性在Nazarov电环化反应。
The Nazarov reaction of pentadienyl cations generated by protonation of either dienones or alkoxytrienes has been examined in detail both experimentally and by DFT calculations. In particular, calculations at the B3LYP/6-311G** level of theory accurately predicted, and accounted for, the outcome of the Bronsted acid catalyzed electrocyclization of 4 pi-electron systems in which one of the double bonds involved in the process was embedded in N- and S-heterocyclic rings. Calculations showed that both heteroatoms are capable of accelerating the ring closure by stabilizing the partial positive charge which develops at C-6 (C-2) in the transition state, with S-heterocyclic derivatives being more reactive than the corresponding N-containing compounds. In general, pentadienyl cations generated by protonation of alkoxytrienes were expected to react faster than those obtained by protonation of the corresponding dienones, as the latter were stabilized by a hydrogen bond. The presence of a substituent on the heterocyclic ring significantly affects the stereoselectivity (torquoselectivity) only in the case of the N-heterocyclic derivatives, in which a 2-alkyl group is axially oriented, providing the cis-2,5-disubstituted isomer only. Instead, with substituted S-heterocyclic compounds, the anticipated torquoselectivity was very low and, in fact, a 3:1 diastereomeric mixture between the trans and cis products was experimentally found after ring closure. For this study, the synthesis of the appropriate N- and S-containing dienones and alkoxytrienes was realized to evaluate the predictivity power of the DFT computations, which was very good in all of the cases examined, both in terms of reactivity and stereoselectivity. The consistency observed between computational and experimental results, therefore, shows the usefulness of DFT calculations at the B3LYP/6-311G** level of theory as a robust instrument for the prediction of reactivity and stereoselectivity in the Nazarov electrocyclic reaction.