Generation of an 4-Isoxazolyl Anion Species: Facile Access to Multifunctionalized Isoxazoles.
A direct functionalization of unsubstituted isoxazole (1) was achieved by generation of 4-isoxazolyl anion species (3). An efficient 4-iodination of isoxazole and halogen-metal exchange reaction using a turbo Grignard reagent (iPrMgCl⋅ LiCl) were essential for the generation of 3, which reacted with various electrophiles to give 4-functionalized isoxazoles in good to high yields. Isoxazolyl boronate, boronic acid, and stannane were also synthesized as useful building blocks from 1. The current methods enabled us to synthesize multi-functionalized isoxazoles by introducing each substituent into the desired positions. Furthermore, total synthesis of triumferol, which was isolated from Triumfetta rhomboidea, was achieved from 1 in only three steps.
Laboratory for Chemistry and Life Science Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, 226-8503, Japan.
Taiki
T
Morita
Laboratory for Chemistry and Life Science Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, 226-8503, Japan. sfuse@res.titech.ac.jp.
Shinichiro
S
Fuse
Laboratory for Chemistry and Life Science Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, 226-8503, Japan. hiro@res.titech.ac.jp.
Hiroyuki
H
Nakamura
Grignard reaction; cross-coupling; halogenation; heterocycles; metalation