Sequential C-H Arylation and Enantioselective Hydrogenation Enables Ideal Asymmetric Entry to the Indenopiperidine Core of an 11-HSD-1 Inhibitor. Academic Article uri icon

abstract

  • A concise asymmetric synthesis of an 11-HSD-1 inhibitor has been achieved using inexpensive starting materials with excellent step-economy at low catalyst loadings. The catalytic enantioselective total synthesis of 1 was accomplished in 7 steps and 38% overall yield aided by the development of an innovative, sequential strategy involving Pd-catalyzed pyridinium C-H arylation and Ir-catalyzed asymmetric hydrogenation of the resulting fused tricyclic indenopyridinium salt highlighted by the use of a unique P,N-ligand (MeO-BoQPhos) with 1000 ppm of [Ir(COD)Cl]2.

published proceedings

  • J Am Chem Soc

altmetric score

  • 8.624

author list (cited authors)

  • Wei, X., Qu, B. o., Zeng, X., Savoie, J., Fandrick, K. R., Desrosiers, J., ... Senanayake, C. H.

citation count

  • 44

complete list of authors

  • Wei, Xudong||Qu, Bo||Zeng, Xingzhong||Savoie, Jolaine||Fandrick, Keith R||Desrosiers, Jean-Nicolas||Tcyrulnikov, Sergei||Marsini, Maurice A||Buono, Frederic G||Li, Zhibin||Yang, Bing-Shiou||Tang, Wenjun||Haddad, Nizar||Gutierrez, Osvaldo||Wang, Jun||Lee, Heewon||Ma, Shengli||Campbell, Scot||Lorenz, Jon C||Eckhardt, Matthias||Himmelsbach, Frank||Peters, Stefan||Patel, Nitinchandra D||Tan, Zhulin||Yee, Nathan K||Song, Jinhua J||Roschangar, Frank||Kozlowski, Marisa C||Senanayake, Chris H

publication date

  • January 2016