Organic N-containing compounds, including amines, are essential components of many biologically and pharmaceutically important molecules. One strategy for introducing nitrogen into substrates with multiple reactive bonds is to insert a monovalent N fragment (nitrene or nitrenoid) into a C–H bond or add it directly to a C=C bond. However, it has been challenging to develop well-defined catalysts capable of promoting predictable and chemoselective aminations solely through reagent control. Herein, we report remarkable chemoselective aminations that employ a single metal (Ag) and a single ligand (phenanthroline) to promote either aziridination or C–H insertion by manipulating the coordination geometry of the active catalysts.
A series of NHC−copper complexes was synthesized and their potential to catalyze 1,3-halogen migration explored. Increasing the steric bulk around the metal drastically improves the lifetime of NHC−CuH species and promotes 1,3-halogen migration of both 2-bromo-and 2-chlorostyrenes through transfer of an aryl halogen to a benzylic carbon with concomitant arene borylation. The NHC-based system displays a broad substrate scope with notable advantages over previously reported phosphine-based catalysts, including complete selectivity for migration versus competing benzylic borylation, increased steric tolerance, efficient aryl chloride migration, and facile formation and characterization of organocopper catalytic intermediates. Experimental evidence and DFT calculations support a mechanism proceeding through dearomatization of a benzyl copper species, followed by a 1,4-halogen shift and borylation of the resulting ArCu(I) intermediate.
The facile generation of benzyl anion equivalents from styrenes has been achieved. A Cu-catalyzed hydroboration is used in conjunction with sterically-induced cleavage of the C-B bond with tBuOK. Quenching this reactive intermediate with heterocumulene electrophiles, including CO2, CS2, isocyanates and isothiocyanates, yields benzylic C-C bond formation. The utility of this methodology was demonstrated in a synthesis of the non-steroidal anti-inflammatory drug (+)-flurbiprofen.
Allene aziridination generates useful bicyclic methylene aziridine scaffolds that can be flexibly transformed into a range of stereochemically complex and densely functionalized amine-containing stereotriads. The scope of this chemistry has been limited by the poor chemoselectivity that often results when typical dinuclear Rh(II) catalysts are employed with homoallenic carbamates. Herein, Ag(I) catalysts that significantly improve the scope and yield of bicyclic methylene aziridines that can be prepared via allene aziridination are described.
A convenient synthesis of α,β-unsaturated imines requiring only an allylic alcohol, an amine and a Ru catalyst has been developed. The use of large excesses of oxidant and the purification of sensitive intermediates can be avoided.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.