Monofluoralkenylierung von Dimethylaminoverbindungen durch Radikal‐Radikal‐Kreuzkupplung

Abstract

Eine neuartige und schwierige Radikal-Radikal-Kreuzkupplung von a-Aminoalkylradikalen mit von gem-Difluoralkenen abgeleiteten Monofluoralkenylradikalen wurde erreicht. Dieses erste Beispiel einer Tandem-C(sp 3 )-H/ C(sp 2 )-F-Bindungsfunktionalisierung über Photoredoxkatalyse mit sichtbarem Licht erçffnet einen leichten und flexiblen Zugang zu privilegierten, tetrasubstituierten Monofluoralkenen unter sehr milden Reaktionsbedingungen. Die besonderen Eigenschaften dieses redoxneutralen Verfahrens bezüglich der Anwendungsbreite,d er Toleranz gegenüber funktionellen Gruppen und Regioselektivität zeigen sich durchd ie Fluoralkenylierungen von komplexen molekularen Architekturen wie dem bioaktiven (+ +)-Filtiazem, Rosiglitazon, Dihydroartemisinin, Oleanolsäure und einem Androsteron-Derivat;d ies sind wichtigen eue a-Amino-C-H-Monofluoralkenylierungen.Hintergrundinformationen zu diesem Beitrag sind unter: http://dx.

Photocatalytic C−F Bond Activation of Fluoroarenes, gem‐Difluoroalkenes and Trifluoromethylarenes

“…[55] Otherwise, the research on visible light induced CÀ F activation of gem-fluoroalkenes has just bloomed since the first report from Hashmi group via CÀ H/CÀ F coupling in 2016 (Scheme 25). [56] The protocol was conducted with PC, Ir[dF(CF 3 ) ppy] 2 (dtbbpy)PF 6 , and bases under blue light irradiation at room temperature. The scope covered symmetric gem-difluoroalkenes 34 attached with different aryl groups (36 a), and asymmetric ones (36 b-36 c) with aryl and alkyl or H albeit with moderate E/Z selectivity.…”

Direct α-Monofluoroalkenylation of Heteroatomic Alkanes via a Combination of Photoredox Catalysis and Hydrogen-Atom-Transfer Catalysis

“…At this stage, desired α-aminoalkyl radical G can be formed via HAT between 2b and radical cation E . Fluoroalkenyl radical H can be generated through SET reduction of 1a ( E 1/2 red = −1.04 V vs SCE) by Ir­(II) complex D ( E 1/2 [*Ir­(III)/Ir­(II)] = −1.37 V vs SCE) and cleavage of the C–F bond. Finally, target product 3ab is generated by selective cross-coupling of radicals G and H .…”

“…6 However, C(sp 3 )−H bond monofluoroalkenylation remains a formidable challenge. Hashmi et al 7 reported a catalytic visible-light-induced photoredox monofluoroalkenylation reaction of tertiary amines at an α-C(sp 3 ) to afford tetrasubstituted monofluoroalkenes (Scheme 1a). Nevertheless, because the reaction is suitable only for tertiary amines, its utility for the synthesis of drugs is severely limited.…”

“…Under irradiation with blue light, the photocatalyst is excited from ground-state Ir(III) species A to excited-state Ir*(III) species B. SET between B (E 1/2 [*Ir(III)/Ir(II)] = +1.21 V vs SCE) 14 and quinuclidine (E p = +1.1 V vs SCE) 15 forms radical cation E and reduced Ir(II) complex D. At this stage, desired α-aminoalkyl radical G can be formed via HAT between 2b and radical cation E. Fluoroalkenyl radical H can be generated through SET reduction of 1a (E 1/2 red = −1.04 V vs SCE) 7 by Ir(II) complex D (E 1/2 [*Ir(III)/Ir(II)] = −1.37 V vs SCE) 14 and cleavage of the C−F bond. Finally, target product 3ab is generated by selective cross-coupling of radicals G and H.…”