Enantioselective Synthesis of -(Hetero)aryl Piperidines through Asymmetric Hydrogenation of Pyridinium Salts and Its Mechanistic Insights. uri icon

abstract

  • Enantioselective synthesis of -aryl and -heteroaryl piperidines is reported. The key step is an iridium-catalyzed asymmetric hydrogenation of substituted N-benzylpyridinium salts. High levels of enantioselectivity up to 99.3:0.7 er were obtained for a range of -heteroaryl piperidines. DFT calculations support an outersphere 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.

published proceedings

  • Org Lett

author list (cited authors)

  • Qu, B. o., Mangunuru, H., Tcyrulnikov, S., Rivalti, D., Zatolochnaya, O. V., Kurouski, D., ... Senanayake, C. H.

citation count

  • 34

complete list of authors

  • Qu, Bo||Mangunuru, Hari PR||Tcyrulnikov, Sergei||Rivalti, Daniel||Zatolochnaya, Olga V||Kurouski, Dmitry||Radomkit, Suttipol||Biswas, Soumik||Karyakarte, Shuklendu||Fandrick, Keith R||Sieber, Joshua D||Rodriguez, Sonia||Desrosiers, Jean-Nicolas||Haddad, Nizar||McKellop, Keith||Pennino, Scott||Lee, Heewon||Yee, Nathan K||Song, Jinhua J||Kozlowski, Marisa C||Senanayake, Chris H

publication date

  • March 2018