Diversity-Oriented Chiral Phosphoric Acid Catalyzed Alkylation of Indolizines with Aminals
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0000-0002-5058-7669 Date
2024
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The Royal Society of Chemistry
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Abstract
Innovations in the pharmaceutical industry and material science drive the need for creating enantiomerically pure heterocyclic molecules with greater complexity and diversity. This study presents methodology to control enantioselective alkylation of indolizines with aminals catalysed by chiral phosphoric acids (CPA), leading to protected indolizylamines achieved in three distinct processes by precise adjustment of reaction conditions. This chemistry can be conducted with excellent enantioselectivity and good yields at both the C1 and C3 position of indolizine. These transformations are scalable and exhibit good functional groups tolerance. The linear free-energy relationship between the property of the catalysts (% buried volume) and alkylation selectivity is demonstrated and a stereoselection model is proposed.
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A.F. Kassir, N. Rad, P. Klochowicz, J.M. Granda, Org. Chem, Front. 2024. http://dx.doi.org/10.1039/D4QO01543F