Fabian Walter M F
Institut für Chemie, Karl-Franzens Universität Graz, Heinrichstrasse 28, A-8010 Graz, Austria.
J Org Chem. 2002 Oct 18;67(21):7475-82. doi: 10.1021/jo026142o.
The site of nucleophilic addition to five-membered heterocyclic 2,3-diones (4-iminomethylfuran-2,3-dione A1 and 4-formyl-pyrrole-2,3-dione B1) is studied by density functional theory calculations (B3LYP/6-31G) with water as the nucleophile. Both uncatalyzed and water-assisted 1,2-addition to the lactone (lactam) and the keto carbonyl group, and conjugate addition to C5 of the heterocycle and the heteroatom of the 4-iminomethyl (formyl) moiety are considered. In addition, concerted and stepwise ring fission of the lactone (lactam) ring is also treated. The effect of solvation (aqueous solution) is taken into account by the polarizable continuum model (PCM) and the Poisson-Boltzmann SCRF method (PB-SCRF), as well as explicit water molecules. Only this latter approach yields meaningful activation free energies. Barriers for addition of H2O increase in the order 1,4-addition to C5 < addition to the lactone (lactam) carbonyl < hydration of the 3-keto group. No reaction path for concerted water-assisted ring opening could be found.
以水作为亲核试剂，通过密度泛函理论计算（B3LYP/6-31G）研究了亲核加成到五元杂环2,3-二酮（4-亚氨基甲基呋喃-2,3-二酮A1和4-甲酰基吡咯-2,3-二酮B1）的位点。考虑了未催化和水辅助的1,2-加成到内酯（内酰胺）和酮羰基，以及共轭加成到杂环的C5和4-亚氨基甲基（甲酰基）部分的杂原子。此外，还处理了内酯（内酰胺）环的协同和逐步开环。通过极化连续介质模型（PCM）和泊松-玻尔兹曼自洽反应场方法（PB-SCRF）以及明确的水分子来考虑溶剂化（水溶液）的影响。只有后一种方法能产生有意义的活化自由能。H2O加成的势垒按以下顺序增加：对C5的1,4-加成 < 对内酯（内酰胺）羰基的加成 < 3-酮基的水合。未发现协同水辅助开环的反应路径。
