Enantioselective Synthesis of α-(Hetero)aryl Piperidines Through Asymmetric Hydrogenation of Pyridinium Salts and Its Mechanistic Insights

Autor:	Keith R. Fandrick, Daniel Rivalti, Nizar Haddad, Marisa C. Kozlowski, Olga V. Zatolochnaya, Suttipol Radomkit, Scott Pennino, Nathan K. Yee, Keith McKellop, Dmitry Kurouski, Jean-Nicolas Desrosiers, Heewon Lee, Chris H. Senanayake, Soumik Biswas, Shuklendu D. Karyakarte, Jinhua J. Song, Bo Qu, Sonia Rodriguez, Hari P. R. Mangunuru, Sergei Tcyrulnikov, Joshua D. Sieber
Jazyk:	angličtina
Rok vydání:	2018
Předmět:	Protonation Pyridinium Compounds 010402 general chemistry Iridium 01 natural sciences Biochemistry Medicinal chemistry Article Catalysis Enamine chemistry.chemical_compound Piperidines Physical and Theoretical Chemistry Molecular Structure 010405 organic chemistry Hydride Aryl Organic Chemistry Asymmetric hydrogenation Enantioselective synthesis Iminium Stereoisomerism 0104 chemical sciences chemistry Models Chemical Pyridinium Hydrogenation Oxidation-Reduction
Popis:	Enantioselective synthesis of α-aryl and α-heteroaryl piperidines is reported. The key step is an iridium-catalyzed asymmetric hydrogenation of substituted N-benzyl pyridinium salts. High levels of enantioselectivity up to 99.3:0.7 er were obtained for a range of α-heteroaryl piperidines. DFT calculations support an outer-sphere dissociative mechanism for the pyridinium reduction. Notably, initial protonation of the final enamine intermediate determines the stereochemical outcome of the transformation rather than hydride reduction of the resultant iminium intermediate.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ea58d5693fceeb4c744ba3de80f4c7e0 https://europepmc.org/articles/PMC5835364/ Zobrazit plný text záznamu