Visible‐Light‐Driven Palladium‐Catalyzed Radical Alkylation of C−H Bonds with Unactivated Alkyl Bromides

Abstract

Reported herein is a novel visible-light photoredox system with Pd(PPh ) as the sole catalyst for the realization of the first direct cross-coupling of C(sp )-H bonds in N-aryl tetrahydroisoquinolines with unactivated alkyl bromides. Moreover, intra- and intermolecular alkylations of heteroarenes were also developed under mild reaction conditions. A variety of tertiary, secondary, and primary alkyl bromides undergo reaction to generate C(sp )-C(sp ) and C(sp )-C(sp ) bonds in moderate to excellent yields. These redox-neutral reactions feature broad substrate scope (>60 examples), good functional-group tolerance, and facile generation of quaternary centers. Mechanistic studies indicate that the simple palladium complex acts as the visible-light photocatalyst and radicals are involved in the process.

Catalysis with Palladium Complexes Photoexcited by Visible Light

“…[28] This reaction proceeded smoothly with ab road scope of alkyl halides,w ith unactivated primary,s econdary, and tertiary alkyl bromides,and even benzyl chlorides,being efficiently coupled with N-aryl-tetrahydroisoquinolines 52 at the a-position (Table 8, 53 a-53 s). [28] This reaction proceeded smoothly with ab road scope of alkyl halides,w ith unactivated primary,s econdary, and tertiary alkyl bromides,and even benzyl chlorides,being efficiently coupled with N-aryl-tetrahydroisoquinolines 52 at the a-position (Table 8, 53 a-53 s).…”

Visible‐Light‐Driven, Copper‐Catalyzed Decarboxylative C(sp3)−H Alkylation of Glycine and Peptides

“…The direct alkylation of C(sp 3 )−H provides a convenient alternative for C(sp 3 )−C(sp 3 ) cross‐coupling. Very recently, the photoinduced alkylation of C(sp 3 )−H was developed by the groups of MacMillan and Yu, using either alkyl bromides or benzyl chlorides as electrophiles. MacMillan and co‐workers also reported its applications in alkylated modification of peptides and pharmaceutical compounds .…”

Katalyse mit durch sichtbares Licht angeregten Palladiumkomplexen

“…[28] Die Reaktion verlief glatt mit einem breiten Substratspektrum an Alkylhalogeniden, wobei nicht aktivierte primäre,sekundäre und tertiäre Alkylbromide und sogar Benzylchloride effizient mit N-Aryltetrahydroisochinolinderivaten 52 an der a-Position gekuppelt wurden (Tabelle 8; 53 a-53 s). [28] Die Reaktion verlief glatt mit einem breiten Substratspektrum an Alkylhalogeniden, wobei nicht aktivierte primäre,sekundäre und tertiäre Alkylbromide und sogar Benzylchloride effizient mit N-Aryltetrahydroisochinolinderivaten 52 an der a-Position gekuppelt wurden (Tabelle 8; 53 a-53 s).…”