186586-70-9Relevant academic research and scientific papers
New strategy for the synthesis of 3-substituted prolines
Karoyan, Philippe,Chassaing, Gerard
, p. 85 - 88 (1997)
Ring formation involving a 5-exo trig cyclization between a zinc enolate and a non activated double bond led to cis diastereoisomer of 3-substituted prolines. This cyclization was achieved with transfer of chirality onto the C-2 carbon when nitrogen was protected by an α-methylbenzyl group. Reprotonation of the lithium enolate of cis derivative yielded the trans diastereoisomer.
Development of a Zinc-Mediated Approach to a 2,3- cis-Pyrrolidine Arginase Inhibitor
He, Cyndi Qixin,Lyons, Thomas W.,Martinot, Theodore A.,Qi, Ji,Shao, Guangxin
, p. 1457 - 1466 (2020/10/12)
This manuscript outlines the development activities toward a robust synthesis of cis-2,3-pyrrolidine via tandem zinc-enolate cyclization/Negishi coupling that proceeds with high diastereoselectivity. The methodology facilitated a gram-scale delivery of the target API and eliminated the need for costly chiral resolutions and inefficient protecting group manipulations. A series of DFT experiments provided a transition-state model that agrees closely with the experimental observations and provides a more in-depth understanding of the observed selectivity.
