Palladium-catalyzed dynamic kinetic asymmetric transformations of vinyl aziridines with nitrogen heterocycles: rapid access to biologically active pyrroles and indoles.
We report that nitrogen heterocycles can serve as competent nucleophiles in the palladium-catalyzed dynamic kinetic asymmetric alkylation of vinyl aziridines. The resulting alkylated products were obtained with high regio-, chemo-, and enantioselectivity. Both substituted 1H-pyrroles and 1H-indoles were successfully employed to give exclusively the branched N-alkylated products. The synthetic utility of this process was demonstrated by applying this method to the preparation of several medicinal chemistry lead compounds and bromopyrrole alkaloids including longamide B, longamide B methyl ester, hanishin, agesamides A and B, and cyclooroidin.
Trost
Barry M
BM
Department of Chemistry, Stanford University, Stanford, California 94305-5080, United States. bmtrost@stanford.edu
Osipov
Maksim
M
Dong
Guangbin
G
D001388:Aziridines / Q000737:chemistry*; D002384:Catalysis; D015195:Drug Design; D006571:Heterocyclic Compounds / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*; D014753:Vinyl Compounds / Q000737:chemistry*
D001388:Aziridines; D006571:Heterocyclic Compounds; D007211:Indoles; D011758:Pyrroles; D014753:Vinyl Compounds; C511002:longamide B; D010165:Palladium; D009584:Nitrogen