Dar'in Dmitry, Kantin Grigory, Bakulina Olga, Inyutina Anna, Chupakhin Evgeny, Krasavin Mikhail
Saint Petersburg State University, Saint Petersburg, 199034 Russian Federation.
Immanuel Kant Baltic Federal University, Kaliningrad 236041 Russian Federation.
J Org Chem. 2020 Dec 4;85(23):15586-15599. doi: 10.1021/acs.joc.0c02356. Epub 2020 Nov 23.
New types of cyclic diazo compounds capable of Rh(II)-catalyzed spirocyclizations with tetrahydrofuran have been discovered. The formation of the spirocyclic framework is thought to proceed the formation of Rh(II) carbene species followed by interaction with the Lewis basic oxygen atom of tetrahydrofuran to give oxonium ylide species. The latter evolves predominantly the Stevens type rearrangement leading to an [ + 1] ring expansion of the tetrahydrofuran moiety, which results in the formation of a medicinally relevant 6-oxa-2-azaspiro[4.5]decane scaffold. The spirocyclization process was often observed in competition with mechanistically distinct C-H insertion into a tetrahydrofuran molecule. This competing process gave compounds based on the 3-(tetrahydrofur-2-yl)pyrrolidine scaffold, which are also relevant from the medicinal chemistry standpoint. These findings enrich the available arsenal of metal-catalyzed spirocyclization methods based on the use of cyclic diazo compounds.
已发现新型环状重氮化合物，其能够与四氢呋喃发生铑（II）催化的螺环化反应。螺环骨架的形成被认为是通过铑（II）卡宾物种的形成，随后与四氢呋喃的路易斯碱性氧原子相互作用生成氧鎓叶立德物种。后者主要通过史蒂文斯型重排进行演化，导致四氢呋喃部分发生[ + 1]环扩展，从而形成具有药物相关性的6-氧杂-2-氮杂螺[4.5]癸烷骨架。螺环化过程常常与机理不同的碳 - 氢插入四氢呋喃分子的反应相互竞争。这种竞争过程生成了基于3-(四氢呋喃-2-基)吡咯烷骨架的化合物，从药物化学角度来看，这些化合物也具有相关性。这些发现丰富了基于环状重氮化合物使用的金属催化螺环化方法的可用手段。
