Intermolecular C–H Amination of Complex Molecules: Insights into the Factors Governing the Selectivity

Transition-metal-catalyzed C–H amination via nitrene insertion allows the direct transformation of a C–H into a C–N bond. Given the ubiquity of C–H bonds in organic compounds, such a process raises the problem of regio- and chemoselectivity, a challenging goal even more difficult to tackle as the complexity of the substrate increases. Whereas excellent regiocontrol can be achieved by the use of an appropriate tether securing intramolecular addition of the nitrene, the intermolecular C–H amination remains much less predictable. This study aims at addressing this issue by capitalizing on an efficient stereoselective nitrene transfer involving the combination of a chiral aminating agent <b>1</b> with a chiral rhodium catalyst <b>2</b>. Allylic C–H amination of terpenes and enol ethers occurs with excellent yields as well as with high regio-, chemo-, and diastereoselectivity as a result of the combination of steric and electronic factors. Conjugation of allylic C–H bonds with the π-bond would explain the chemoselectivity observed for cyclic substrates. Alkanes used in stoichiometric amounts are also efficiently functionalized with a net preference for tertiary equatorial C–H bonds. The selectivity, in this case, can be rationalized by steric and hyperconjugative effects. This study, therefore, provides useful information to better predict the site of C–H amination of complex molecules

Efficient Fluoride-Catalyzed Conversion of CO₂ to CO at Room Temperature

A protocol for the efficient and selective reduction of carbon dioxide to carbon monoxide has been developed. Remarkably, this oxygen abstraction step can be performed with only the presence of catalytic cesium fluoride and a stoichiometric amount of a disilane in DMSO at room temperature. Rapid reduction of CO₂ to CO could be achieved in only 2 h, which was observed by pressure measurements. To quantify the amount of CO produced, the reduction was coupled to an aminocarbonylation reaction using the two-chamber system, COware. The reduction was not limited to a specific disilane, since (Ph₂MeSi)₂ as well as (PhMe₂Si)₂ and (Me₃Si)₃SiH exhibited similar reactivity. Moreover, at a slightly elevated temperature, other fluoride salts were able to efficiently catalyze the CO₂ to CO reduction. Employing a nonhygroscopic fluoride source, KHF₂, omitted the need for an inert atmosphere. Substituting the disilane with silylborane, (pinacolato)­BSiMe₂Ph, maintained the high activity of the system, whereas the structurally related bis­(pinacolato)­diboron could not be activated with this fluoride methodology. Furthermore, this chemistry could be adapted to ¹³C-isotope labeling of six pharmaceutically relevant compounds starting from Ba¹³CO₃ in a newly developed three-chamber system