Pivalophenone imine as a benzonitrile surrogate for directed C–H bond functionalization

Abstract

Pivalophenone N–H imine undergoes facile directed C–H functionalization and subsequent iminyl radical fragmentation, thus efficiently affording ortho-functionalized benzonitriles.

Iron‐Catalyzed ortho C−H Arylation and Methylation of Pivalophenone N−H Imines

“…We previously demonstrated that ortho ‐arylated and alkylated pivalophenone N−H imines efficiently undergo fragmentation of the pivaloyl imine moiety into a cyano group under peroxide photolysis or aerobic copper catalysis . The same transformation proved feasible for the methylated products, and conversion of 3 c into the ortho ‐methylated aryl nitrile 4 was achieved in good yield under aerobic copper catalysis (Scheme ) …”

“…Recently, we have demonstrated that pivaloyl N−H imine serves as an excellent directing group for cobalt‐catalyzed ortho C−H functionalization reactions such as hydroarylation to alkenes and alkylation/arylation with the corresponding organic halides . The imine functionality can be readily transformed into a cyano group, thus allowing facile preparation of ortho ‐functionalized benzonitriles . Given this background and other reports on transition‐metal‐catalyzed, N−H imine‐directed C−H functionalization, we became interested in the competence of pivaloyl N−H imine as a monodentate directing group for the iron‐catalyzed C−H/C−M coupling manifold.…”

“…The same was the case for 2‐naphthyl imine, which underwent exclusive phenylation at the 3‐position (see 2 pa ). It is worthwhile to note the difference between this regioselectivity trend and that of the cobalt‐catalyzed arylation with aryl chloride, which is susceptible to the secondary directing effect of meta ‐oxygen or fluorine substituents. For example, the cobalt‐catalyzed arylation of 3,4‐methylenedioxyphenyl imine took place on the ortho ‐position proximal to the oxygen atom to afford the regioisomer of 2 na .…”

Synthesis of Functionalized Nitriles by Microwave‐Promoted Fragmentations of Cyclic Iminyl Radicals

“…In contrast, fragmentations of cyclic iminyl radicals have been less studied. These processes, which until recently have been observed mainly in the context of nitrile translocations, produce a synthetically useful nitrile tethered to an alkyl radical. However, rapid reduction of the alkyl radical by a hydrogen atom donor that is often present in the reaction mixture (e.g., Bu 3 SnH) has precluded further functionalization.…”

Jenseits von Friedel und Crafts: dirigierte Alkylierung von C‐H‐Bindungen in Arenen

“…Dieses Verfahren wurde weiter auf die Umsetzung von Pivalophenon-N-H-Iminen ausgeweitet, die sich als hervorragende Benzonitrilsurrogate fürdirigierte C-H-Alkylierungen erwiesen, bei denen die entsprechenden Benzonitrile in einem Folgeschritt entweder durch Bestrahlung in Gegenwart eines Peroxids oder durch Reaktion mit einer katalytischen Mengen an Kupfer(II)-acetat unter aeroben Bedingungen hergestellt wurden. [67] Weitere Untersuchungen in der Gruppe von Ackermann zur rutheniumkatalysierten Alkylierung von Iminen gipfelten in der Entwicklung einer hochregioselektiven meta-Alkylierung mit sekundären und tertiären Alkylbromiden (Schema 12). [68] Mit einem Katalysesystem, das dem mit primären Alkylbromiden verwendeten stark ähnelte,e rfolgte eine saubere meta-selektive Alkylierung von TMP-Iminen.…”