Hydroxylamin‐abgeleitetes Reagenz als duales Oxidationsmittel und Aminogruppendonor für die eisenkatalysierte Herstellung von ungeschützten Sulfinamiden aus Thiolen

Abstract

Es wurde eine eisenkatalysierte Reaktion für die selektive Umwandlung von Thiolen (‐SH) in Sulfinamide (‐SONH2) durch direkte Übertragung von ‐O und freien ‐NH2‐Gruppen entwickelt. Die Reaktion läuft unter milden Bedingungen unter Verwendung eines luftstabilen, von Hydroxylamin abgeleiteten Reagenz ab, weist eine breite Toleranz gegenüber funktionellen Gruppen auf, ist skalierbar und verläuft ohne die Verwendung eines Edelmetallkatalysators oder eines zusätzlichen Oxidationsmittels. Diese neuartige, praktische Reaktion führt zur Bildung von zwei verschiedenen neuen Bindungen (S=O und S−N) in einem einzigen Schritt, um chemoselektiv wertvolle, ungeschützte Sulfinamidprodukte zu bilden. Vorläufige mechanistische Studien implizieren die Rolle des alkoholischen Lösungsmittels als Sauerstoffatomdonor.

A Combined Spectroscopic and Computational Study on the Mechanism of Iron-Catalyzed Aminofunctionalization of Olefins Using Hydroxylamine Derived N–O Reagent as the “Amino” Source and “Oxidant”

“…The unusual electronic structure of Int II , with an elongated Fe–N bond, makes it highly efficient for participating in the N -transfer reaction to styrenyl olefins (Scheme , Figure ), and in the presence of nucleophilic solvent, regioselectively forms aminoethers, which are versatile intermediates for the synthesis of bioactive compounds. Besides unravelling the mechanism for the aminomethoxylation reaction, the mechanistic cycle proposed above, and the electronic structure of the two new iron–nitrogen intermediates reported in this study, should also provide key reference points for understanding the mechanism of other iron catalyzed aminofunctionalization reactions of organic molecules by the hydroxyl amine derived reagent (PivONH 3 OTf) reported in literature. − Int I , a high spin Fe­(III)- N -acyloxy species, has a resemblance to high spin Fe­(III)-alkyl/acyl peroxo intermediates known in the literature, formed during the reaction of an Fe­(II) catalyst and alkyl/aryl peroxides. Though Fe­(NH) complexes as isoelectronic surrogates to Fe­(O) functionalities are reported in literature, , to the best of our knowledge this is the first report of a high-spin Fe­(III)- N -acyloxy intermediate as a synthetic analogue of the Fe­(III)-alkyl/acyl peroxo intermediate.…”

“…In order to address these issues, and inspired by the seminal work from Minisci, Morandi and co-workers have developed a research program focused on iron-catalyzed direct synthesis of unprotected amines (aminofunctionalization of alkenes) using hydroxylamine derived reagents (Scheme , left panel). − The versatile reactivity of the iron-catalyzed aminofunctionalization was also successfully exploited for heteroatom amination (Scheme , left panel). , Subsequently, Arnold and co-workers broadened the utility of these hydroxylamine-derived reagents to mimic the non-natural nitrene transfer reaction for enantioselective amination of styrenyl olefins, as well as −C–H bonds of alkanes, catalyzed by engineered hemoproteins (Scheme , right panel). , However, despite the successful utilization of the iron-catalyzed amination reaction on various organic substrates, the mechanistic pathway and nature of the active species responsible for the aminofunctionalization reaction, whether a free aminium organic radical (NH 3 +• ) − or any iron-based aminating species is involved ,,− remains unknown. To date there has been no spectroscopic or theoretical report on the mechanistic details of the iron-catalyzed reaction by these novel hydroxyl-amine derived reagents.…”

“…To date there has been no spectroscopic or theoretical report on the mechanistic details of the iron-catalyzed reaction by these novel hydroxyl-amine derived reagents. However, control studies have strongly implicated the key role of iron in the amination reaction. − …”