Rhodium‐Catalyzed Remote C‐8 Alkylation of Quinolines with Activated and Unactivated Olefins: Mechanistic Study and Total Synthesis of EP4 Agonist

Reported herein is a rhodium(III)‐catalyzed regioselective distal C(sp2)‐H bond alkylation of quinoline N‐oxides using olefins as alkyl source and N‐oxide as the traceless directing group. The reaction exhibits broad substrate scope with excellent selectivity for C‐8 position and good yields of alkylated products. The usefulness of the developed catalytic protocol is established by synthesis of EP4 agonist. In mechanistic study, C‐8 olefinated quinoline was identified as the reaction intermediate, which gets reduced to desired C‐8 alkylated product in the presence of a rhodium(I) species (produced from rhodium(III) during reaction) and formic acid. Formic acid is produced from dimethylformamide in the presence of silver tetrafluoroborate.