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Enantioselective and Regiodivergent Synthesis of Propargyl‐ and Allenylsilanes through Catalytic Propargylic C−H Deprotonation

Jin Zhu, Hengye Xiang, Hai Won Chang, James C. Corcoran, Ruiqi Ding, Yue Xia, Peng Liu, Yiming Wang

2024Angewandte Chemie International Edition14 citationsDOIOpen Access PDF

Abstract

Abstract We report a highly enantioselective intermolecular C−H bond silylation catalyzed by a phosphoramidite‐ligated iridium catalyst. Under reagent‐controlled protocols, propargylsilanes resulting from C(sp 3 )−H functionalization, as well the regioisomeric and synthetically versatile allenylsilanes, could be obtained with excellent levels of enantioselectivity and good to excellent control of propargyl/allenyl selectivity. In the case of unsymmetrical dialkyl acetylenes, good to excellent selectivity for functionalization at the less‐hindered site was also observed. A variety of electrophilic silyl sources (R 3 SiOTf and R 3 SiNTf 2 ), either commercial or in situ ‐ generated, were used as the silylation reagents, and a broad range of simple and functionalized alkynes, including aryl alkyl acetylenes, dialkyl acetylenes, 1,3‐enynes, and drug derivatives were successfully employed as substrates. Detailed mechanistic experiments and DFT calculations suggest that an η 3 ‐propargyl/allenyl Ir intermediate is generated upon π‐complexation‐assisted deprotonation and undergoes outer‐sphere attack by the electrophilic silylating reagent to give propargylic silanes, with the latter step identified as the enantiodetermining step.

Topics & Concepts

PropargylChemistryEnantioselective synthesisSilylationElectrophileDeprotonationCombinatorial chemistryReagentSilanesRegioselectivityCatalysisTriple bondSelectivityArylOrganic chemistryAlkylMedicinal chemistryDouble bondSilaneIonCatalytic C–H Functionalization MethodsCatalytic Cross-Coupling ReactionsOrganoboron and organosilicon chemistry
Enantioselective and Regiodivergent Synthesis of Propargyl‐ and Allenylsilanes through Catalytic Propargylic C−H Deprotonation | Litcius