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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Palladium-catalysed imidoylative spirocyclization of 3-(2-isocyanoethyl)indoles
Shi Tang1, Shumin Ding2, Dan Li2
1China Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, P. R. China.
Abstract:
A palladium-catalysed construction of spiroindolines through dearomative spirocyclization of 3-(2-isocyanoethyl)indoles has been developed. 2'-Aryl-, vinyl-, and alkyl-substituted spiroindolines could be accessed under mild conditions with excellent functional group tolerance. C1-tethered oxindole- and indole-spiroindoline bisheterocycles were generated in high yields via alkene/allene insertion and an imidoylative spirocyclization cascade. Additionally, a tandem dearomatization of two different indoles was realized with N-(2-bromobenzoyl)indoles as the electrophilic coupling partner of 3-(2-isocyanoethyl)indoles, affording polyindoline - spiroindoline bisheterocyclic scaffolds conveniently. Under the catalysis of Pd(OAc)2 and a spinol-derived phosphoramidite ligand, chiral spiroindolines were successfully accessed with up to 95% yield and 85% ee.
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The reaction begins with transferring a proton from the acid catalyst to one of the hydroxyl groups, producing an oxonium ion.