Functionalization at the α-position of carbonyl compounds has classically relied on enolate chemistry. As a result, the generation of a new C–X bond, where X is more electronegative than carbon requires an oxidation event. Herein we show that, by rendering the α-position of amides electrophilic through a mild and chemoselective umpolung transformation, a broad range of widely available oxygen, nitrogen, sulfur, and halogen nucleophiles can be used to generate α-functionalized amides. More than 60 examples are presented to establish the generality of this process, and calculations of the mechanistic aspects underline a fragmentation pathway that accounts for the broadness of this methodology.

We report a method for the selective α,β‐dehydrogenation of amides in the presence of other carbonyl moieties under mild conditions. Our strategy relies on electrophilic activation coupled to in situ selective selenium‐mediated dehydrogenation. The α,β‐unsaturated products were obtained in moderate to excellent yields, and their synthetic versatility was demonstrated by a range of transformations. Mechanistic experiments suggest formation of an electrophilic SeIV species.

In comparison to the extensively studied metal‐catalyzed hydroamination reaction, hydroaminomethylation has received significantly less attention despite its considerable potential to streamline amine synthesis. State‐of‐the‐art protocols for hydroaminomethylation of alkenes rely largely on transition‐metal catalysis, enabling this transformation only under highly designed and controlled conditions. Here we report a broadly applicable, acid‐mediated approach to the hydroaminomethylation of unactivated alkenes and alkynes. This methodology employs cheap, readily available, and bench‐stable reactants and affords the desired amines with excellent functional group tolerance and impeccable regioselectivity. The broad scope of this transformation, as well as mechanistic investigations and in situ domino functionalization reactions are reported.

The development of reactions converting alkenes and alkynes into valuable building blocks remains one of the main goals of synthetic chemistry. Herein, we present the leveraging of highly electrondeficient iminium ions, rare and fleeting intermediates, into a general amine synthesis. This enables the preparation of amines bearing e.g. valuable α-trifluoromethyl moieties under mild conditions. This broad concept is highlighted by the late-stage amination of quinine into a biologically interesting new analogue.

Im Vergleichz ur vielbeschriebenen metallkatalysierten Hydroaminierung hat die Hydroaminomethylierung, trotz ihres Potenzials in der Aminsynthese,i nd er Literatur bedeutend weniger Aufmerksamkeit erfahren. Gängige Methoden zur Hydroaminomethylierung von Alkenen bençtigen Übergangsmetallkatalysatoren und ermçglichen diese Reaktion nur unter speziellen und wohlkontrollierten Bedingungen. Diese Arbeit stellt einen allgemeinen, säurevermittelten Zugang zu Hydroaminomethylierungsreaktionen von nichtaktivierten Alkenen und Alkinen vor.D ie Verwendung günstiger,l eichte rhältlicher und stabiler Reagenzien, sowie die breite Substratpalette und ausgezeichnete Regioselektivität machen diese Reaktion zu einer attraktiven alternativen Aminsynthese.