Premium
Rhodium‐Catalyzed Remote C‐8 Alkylation of Quinolines with Activated and Unactivated Olefins: Mechanistic Study and Total Synthesis of EP4 Agonist
Author(s) -
Sharma Ritika,
Kumar Inder,
Kumar Rakesh,
Sharma Upendra
Publication year - 2017
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201700542
Subject(s) - chemistry , rhodium , alkylation , quinoline , regioselectivity , formic acid , catalysis , dimethylformamide , alkyl , medicinal chemistry , organic chemistry , combinatorial chemistry , solvent
Reported herein is a rhodium(III)‐catalyzed regioselective distal C(sp 2 )‐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.