Coupling N–H Deprotonation, C–H Activation, and Oxidation: Metal-Free C(sp³)–H Aminations with Unprotected Anilines

Abstract

An intramolecular oxidative C(sp)-H amination from unprotected anilines and C(sp)-H bonds readily occurs under mild conditions using t-BuOK, molecular oxygen and N,N-dimethylformamide (DMF). Success of this process, which requires mildly acidic N-H bonds and an activated C(sp)-H bond (BDE < 85 kcal/mol), stems from synergy between basic, radical, and oxidizing species working together to promote a coordinated sequence of deprotonation: H atom transfer and oxidation that forges a new C-N bond. This process is applicable for the synthesis of a wide variety of N-heterocycles, ranging from small molecules to extended aromatics without the need for transition metals or strong oxidants. Computational results reveal the mechanistic details and energy landscape for the sequence of individual steps that comprise this reaction cascade. The importance of base in this process stems from the much greater acidity of transition state and product for the 2c,3e C-N bond formation relative to the reactant. In this scenario, selective deprotonation provides the driving force for the process.

Upconversion of Reductants

“…We will start with the role of upconversion in CH aminations with unprotected anilines (Scheme ). This reaction proceeds through a sequence of N‐H deprotonation, radical C−H‐bond activation, and oxidation . This process provides an example of upconversion where the driving force is provided by bond formation and where a potent reactant created by chemical upconversion is intercepted by an external oxidant.…”

Synthesis of π‐Functional Molecules through Oxidation of Aromatic Amines

“…In this case, molecular oxygen worked as the oxidant and only tBuOK in DMFsolution was used. [23] This reactionp roceeded through reductant upconversion including CÀHb ond activation,w hich lowers the Gibbs free energy of the intramolecular CÀNb ond formation. [24] The oxidative intramolecular fusion of amino substituents has been employed also in porphyrinc hemistry.F or example, Osuka et al reportedt he synthesis of a1 ,5-naphthyridinefused porphyrin dimer 13 (Scheme 8).…”

Hochkonversion von Reduktionsmitteln

“…[35] Dieser Prozess liefert ein Beispiel füre ine Hochkonversion, bei der die treibende Kraft durch die Bindungsbildung bereitgestellt wird und bei der ein potenter Reaktant, der durch chemische Hochkonversion erzeugt wird, von einem externen Oxidationsmittel abgefangen wird. Diese Reaktion verläuft entlang folgender Sequenz:N -H-Deprotonierung,R adikal-C-H-Bindungsaktivierung und Oxidation.…”

“…Diese Reaktion verläuft entlang folgender Sequenz:N -H-Deprotonierung,R adikal-C-H-Bindungsaktivierung und Oxidation. [35]…”