342793-00-4Relevant articles and documents
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.
Dual mechanism of zinc-proline catalyzed aldol reactions in water
Kofoed, Jacob,Darbre, Tamis,Reymond, Jean-Louis
, p. 1482 - 1484 (2008/02/11)
The aldol reaction of acetone with aldehydes in aqueous medium under catalysis by zinc-proline (Zn(l-Pro)2) and secondary amines such as proline, (2S,4R)-4-hydroxyproline (Hyp) and (S)-(+)-1-(2-pyrrolidinomethyl) pyrrolidine (PMP) is shown to proceed by an enamine mechanism, as evidenced by reductive trapping of the iminium intermediate, while the aldol reaction of dihydroxyacetone (DHA) under catalysis by zinc-proline and by general bases such as N-methylmorpholine (NMM) is shown to occur under rate-limiting deprotonation of the α-carbon and formation of an enolate intermediate. The Royal Society of Chemistry 2006.