Levandowski Brian J, Graham Brian J, Abularrage Nile S, Raines Ronald T
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States.
J Phys Org Chem. 2024 Sep;37(9). doi: 10.1002/poc.4642. Epub 2024 Jun 7.
The condensation of 1,3-diketones with hydrazine to access 4-pyrazoles is a well-established synthetic route that travels through a 4-pyrazol-1-ium intermediate. In the route to a 3,5-diphenyl-4-pyrazole containing a cyclobutane spirocycle, density functional theory calculations predict and experiments show that the protonated intermediate undergoes a rapid 1,5-sigmatropic shift to form a tetrahydrocyclopenta[]pyrazole. Replacing the 3,5-diphenyl groups with 2-furanyl groups decreases the calculated rate of the 1,5-sigmatropic shift by 6.2 × 10-fold and enables the isolation of new spirocyclic 4-pyrazoles for click chemistry.
1,3 - 二酮与肼缩合以制备4 - 吡唑是一条成熟的合成路线，该路线会经过一个4 - 吡唑 - 1 - 鎓中间体。在通往含有环丁烷螺环的3,5 - 二苯基 - 4 - 吡唑的路线中，密度泛函理论计算预测并经实验表明，质子化中间体经历快速的1,5 - 西格玛迁移以形成四氢环戊并[]吡唑。用2 - 呋喃基取代3,5 - 二苯基会使计算得到的1,5 - 西格玛迁移速率降低6.2×10倍，并能够分离出新的用于点击化学的螺环4 - 吡唑。
