Orel Vladimir B, Vitkovskaya Nadezhda M, Bobkov Alexander S, Semenova Nadezhda V, Schmidt Elena Yu, Trofimov Boris A
Laboratory of Quantum-Chemical Modeling of Molecular Systems, Irkutsk State University, 1 K. Marx Street, 664003 Irkutsk, Russian Federation.
A.E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 1 Favorsky Street, 664033 Irkutsk, Russian Federation.
J Org Chem. 2021 Jun 4;86(11):7439-7449. doi: 10.1021/acs.joc.1c00388. Epub 2021 May 20.
The mechanism of aldol condensation of ketones in KOH/DMSO superbasic media has been investigated using the B2PLYP(D2)/6-311+G**//B3LYP/6-31+G* quantum-chemical approach. It is found that the interaction of three ketone molecules resulting in the formation of the cyclohex-2-enone structure [isophorone or 3,5-dicyclohexyl-5-methylspiro(5.5)undec-2-en-1-one] is thermodynamically more favorable than the interaction of two, three, or four molecules of ketone, resulting in the formation of linear products of the condensation. The formation of the condensation products with the isophorone skeleton can significantly hinder the cascade reactions of ketones with acetylenes [to afford 6,8-dioxabicyclo(3.2.1)octanes or acylcyclopentenols] promoted by superbases. In particular, the kinetically more preferable reactions of autovinylation of 2-methyl-3-butyn-2-ol and autocondensation of acetone are the reasons why interaction of acetone with acetylene does not lead to the products of the cascade assemblies. The predominant formation of the products of these side reactions is confirmed experimentally.
采用B2PLYP(D2)/6 - 311 + G**//B3LYP/6 - 31 + G*量子化学方法，研究了酮在KOH/DMSO超强碱介质中的羟醛缩合反应机理。研究发现，三个酮分子相互作用形成环己 - 2 - 烯酮结构（异佛尔酮或3,5 - 二环己基 - 5 - 甲基螺(5.5)十一碳 - 2 - 烯 - 1 - 酮）在热力学上比两个、三个或四个酮分子相互作用形成线性缩合产物更有利。具有异佛尔酮骨架的缩合产物的形成会显著阻碍超强碱促进的酮与乙炔的级联反应（生成6,8 - 二氧杂双环(3.2.1)辛烷或酰基环戊烯醇）。特别是，2 - 甲基 - 3 - 丁炔 - 2 - 醇的自乙烯基化和丙酮的自缩合在动力学上更优先发生反应，这就是丙酮与乙炔相互作用不会生成级联组装产物的原因。这些副反应产物的主要形成已通过实验得到证实。
