1429301-75-6Relevant academic research and scientific papers
Zinc catalyzed and mediated asymmetric propargylation of trifluoromethyl ketones with a propargyl boronate
Fandrick, Daniel R.,Reeves, Jonathan T.,Bakonyi, Johanna M.,Nyalapatla, Prasanth R.,Tan, Zhulin,Niemeier, Oliver,Akalay, Deniz,Fandrick, Keith R.,Wohlleben, Wolfgang,Ollenberger, Swetlana,Song, Jinhua J.,Sun, Xiufeng,Qu, Bo,Haddad, Nizar,Sanyal, Sanjit,Shen, Sherry,Ma, Shengli,Byrne, Denis,Chitroda, Ashish,Fuchs, Victor,Narayanan, Bikshandarkoil A.,Grinberg, Nelu,Lee, Heewon,Yee, Nathan,Brenner, Michael,Senanayake, Chris H.
, p. 3592 - 3615 (2013/05/23)
The development of zinc-mediated and -catalyzed asymmetric propargylations of trifluoromethyl ketones with a propargyl borolane and the N-isopropyl-l-proline ligand is presented. The methodology provided moderate to high stereoselectivity and was successfully applied on a multikilogram scale for the synthesis of the Glucocorticoid agonist BI 653048. A mechanism for the boron-zinc exchange with a propargyl borolane is proposed and supported by modeling at the density functional level of theory. A water acceleration effect on the zinc-catalyzed propargylation was discovered, which enabled a catalytic process to be achieved. Reaction progress analysis supports a predominately rate limiting exchange for the zinc-catalyzed propargylation. A catalytic amount of water is proposed to generate an intermediate that catalyzes the exchange, thereby facilitating the reaction with trifluoromethyl ketones.
