Hadj Mohamed Slim, Trabelsi Mahmoud, Champagne Benoît
Laboratory of Natural Substances, Faculty of Sciences, University of Sfax , 3038 Sfax, Tunisia.
Laboratory of Theoretical Chemistry, Theoretical and Structural Physical Chemistry Unit, University of Namur , rue de Bruxelles, 61, B-5000 Namur, Belgium.
J Phys Chem A. 2016 Jul 21;120(28):5649-57. doi: 10.1021/acs.jpca.6b02588. Epub 2016 Jul 5.
The uncatalyzed Mukaiyama aldol reaction between C,O,O-tris(trimethylsilyl)ketene acetal and aldehydes bearing alkyl, vinyl, and aromatic substituents has been studied theoretically using density functional theory with the M06-2X exchange-correlation functional. These DFT calculations mostly demonstrate that (i) the syn product is both kinetically and thermodynamically favored, (ii) the diastereoselectivity of the uncatalyzed reaction is larger than observed for the reaction catalyzed by HgI2 and it is inverted with respect to the latter, (iii) solvents with larger dielectric constants increase the activation barrier but reduce the diastereoselectivity, (iv) the concerted reaction is preferred over the stepwise reaction, and (v) the OSiMe3 group in geminal lowers the activation barrier and increases the energy of reaction. Analyzing the concerted mechanism unravels four types of cyclic transition states, two pro-anti and two pro-syn. Then, the relative energy of the most stable transition state of each type as well as of the corresponding anti and syn products shows that the syn reaction path is located at lower Gibbs enthalpy than the anti reaction path for all substituents.
采用密度泛函理论结合M06 - 2X交换相关泛函，对C,O,O - 三（三甲基硅基）乙烯酮缩醛与带有烷基、乙烯基和芳基取代基的醛之间的无催化 Mukaiyama 羟醛反应进行了理论研究。这些密度泛函理论计算大多表明：（i）顺式产物在动力学和热力学上均占优势；（ii）无催化反应的非对映选择性大于HgI₂催化反应所观察到的，且与后者相反；（iii）介电常数较大的溶剂会增加活化能垒，但会降低非对映选择性；（iv）协同反应优于分步反应；（v）偕位的OSiMe₃基团会降低活化能垒并增加反应能量。对协同机理的分析揭示了四种类型的环状过渡态，两种亲反式和两种亲顺式。然后，每种类型最稳定过渡态以及相应的反式和顺式产物的相对能量表明，对于所有取代基，顺式反应路径的吉布斯自由能比反式反应路径更低。
