Ligand-Accelerated Catalysis in Scandium(III)-Catalyzed Asymmetric Spiroannulation Reactions

• Published in: ACS catalysis Vol. 12; no. 6; pp. 3524 - 3533
• Main Authors: Ball-Jones, Nicolas R, Cobo, Angel A, Armstrong, Brittany M, Wigman, Benjamin, Fettinger, James C, Hein, Jason E, Franz, Annaliese K
• Format: Journal Article
• Language: English
• Published: American Chemical Society 18.03.2022
• Subjects: scandium; reaction heat flow calorimetry; mechanism; Lewis acid catalysis; in situ infrared spectroscopy
• ISSN: 2155-5435; 2155-5435
• DOI: 10.1021/acscatal.1c05768

A mechanism for the scandium-catalyzed asymmetric allylsilane annulation reaction is proposed and supported by reaction heat flow calorimetry, NMR, and in situ infrared spectroscopy. The nature of a scandium­(III)–PyBox/BArF catalyst is probed using reaction calorimetric analysis, which reveals a complex interplay between in-solution and precipitated catalyst species. The scandium­(III)–PyBox/BArF catalyst is minimally soluble until the addition of a bidentate electrophile. The optimal reaction rate is dependent on precomplexation of the catalyst, order of complexation of the catalyst components, and delayed addition of nucleophile. The formation of the active catalyst proceeds through a bimolecular combination of scandium­(III) with a BArF anion, followed by complexation with PyBox ligand, where the ligand-dependent rate and selectivity are observed. Notably, ligand-accelerated catalysis is observed, attributed to the ligand reducing off-cycle oligomerization of allylsilane. The role of BArF is discussed with a specific focus on the source of counterion in the reaction rate and enantioselectivity. We also report the formation of a mechanistically relevant fused tetrahydropyranindole produced upon the reaction of an allylsilane with alkylidene oxindole. In situ infrared spectroscopy demonstrates ligand-dependent acceleration where sterically demanding ligands perform with a faster relative reaction rate.