Synthesis of enantioenriched unprotected amines by an enantioselective copper-catalyzed addition reaction to nitriles: application to natural product and medicinal chemistry
Final Report Abstract
Taken together, these examples highlight the importance of methodology development as well as its application to total synthesis. The second stage of the Cu-catalyzed enantioselective addition of allenes to nitriles has proved to be a very versatile methodology to access ketones bearing an α-stereocenter as well as the corresponding syn- and anti-alcohols (instead of secondary amines as first disclosed). As was demonstrated, the alkenyl-B(pin) moiety has synthetic utility as a synthon for a terminal alkene, a methyl ketone or a carboxylic acid. The total synthesis of dolabelide C highlights the difference between the comparatively nonfunctionalized substates in methodology development and the challenge of more oxidized, aliphatic substrates often encountered in total synthesis. It therefore comes as no surprise that synthesis of the oxygenated stereodiads and -triads commonly found in biologically active polyketides still largely relies on auxiliaries (Myers’ pseudoephenamine), preformed chiral reagents (Roush-Hoffmann boronate) or expensive precious metal catalyst complexes (Krische’s iridium catalyst), providing a strong incentive for the development of catalytic enantioselective approaches that rely on earth-abundant, commercially available catalysts.
Publications
- „Different Strategies for Designing Dual-Catalytic Enantioselective Processes: From Fully Cooperative to Non-cooperative Systems“ J. Am. Chem. Soc. 2019, 141, 17952
Filippo Romiti, Juan del Pozo, Paulo H. S. Paioti, Stella A. Gonsales, Xinghan Li, Felix W. W. Hartrampf, and Amir H. Hoveyda
(See online at https://doi.org/10.1021/jacs.9b05464)
