1034497-91-0Relevant academic research and scientific papers
Enantioselective Pd-catalyzed α-arylation of N-Boc-pyrrolidine: The key to an efficient and practical synthesis of a glucokinase activator
Klapars, Artis,Campos, Kevin R.,Waldman, Jacob H.,Zewge, Daniel,Dormer, Peter G.,Chen, Cheng-Yi
, p. 4986 - 4993 (2008/12/21)
(Chemical Equation Presented) A short and practical synthesis of glucokinase activator 1 was achieved utilizing a convergent strategy involving SNAr coupling of activated aryl fluoride 11 with hydroxypyridine 9. The key to the success of the synthesis was the development of a novel method for enantioselective formation of α-arylpyrrolidines during the course of the project. In this method, (-)-sparteine-mediated enantioselective lithiation of N-Boc-pyrrolidine was followed by in situ transmetalation to zinc and Pd-catalyzed coupling with aryl bromide 3, proceeding in 92% ee. This transformation allowed the preparation of compound 1 in a 31% overall yield over six steps.
