Phosphoramidite Gold(I)-Catalyzed Diastereo- and Enantioselective Synthesis of 3,4-Substituted Pyrrolidines
Ana Z. González, Diego Benítez, Ekaterina Tkatchouk, William A. Goddard III, F. Dean Toste
Abstract
In this article the utility of phosphoramidite ligands in enantioselective AuI catalysis was explored in the development of highly diastereo- and enantioselective AuI-catalyzed cycloadditions of allenenes. A Au^I-catalyzed synthesis of 3,4-disubstituted pyrrolidines and γ-lactams is described. This reaction proceeds through the enantioselective AuI-catalyzed cyclization of allenenes to form a carbocationic intermediate that is trapped by an exogenous nucleophile, resulting in the highly diastereoselective construction of three contiguous stereogenic centers. A computational study (DFT) was also performed to gain some insight into the underlying mechanisms of these cycloadditions. The utility of this new methodology was demonstrated through the formal synthesis of (−)-isocynometrine.
Group Members
González, A. Z., Benítez, D., Tkatchouk, E., III, W. A. G., & Toste, F. D. (2011). Phosphoramidite Gold(I)-Catalyzed Diastereo- and Enantioselective Synthesis of 3,4-Substituted Pyrrolidines. *J. Am. Chem. Soc.*, *133*(14), 5500-5507.